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UniProtKB/Swiss-Prot P51587: Variant p.Leu2510Pro

Breast cancer type 2 susceptibility protein
Gene: BRCA2
Chromosomal location: 13q12.3
Variant information

Variant position:  2510
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Leucine (L) to Proline (P) at position 2510 (L2510P, p.Leu2510Pro).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Fanconi anemia complementation group D1 (FANCD1) [MIM:605724]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269|PubMed:12065746, ECO:0000269|PubMed:14670928, ECO:0000269|PubMed:16825431, ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:23108138}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In FANCD1; hypersensitive to DNA damage; disrupts interaction with SEM1; decreased homology-directed repair activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  2510
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  3418
The length of the canonical sequence.

Location on the sequence:   IQDMRIKKKQRQRVFPQPGS  L YLAKTSTLPRISLKAAVGGQ
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         IQDMRIKKKQRQRVFPQPGSLYLAKTSTLPRISLKAAVGGQ

Mouse                         LQDMRIKNKERRHLRLQPGSLYLTKSSTLPRISLQAAVGDR

Rat                           LQDIRIKNKERHHLCPQPGSLYLTKSSTLPRISLQAAVGDS

Cat                           IQDMRIREKRKQHIFPQPGSLFLAKTSTVPRISLRVAVEGR

Drosophila                    IEHFK------------------------------------

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 3418 Breast cancer type 2 susceptibility protein
Region 2350 – 2545 Interaction with FANCD2
Region 2481 – 2832 Interaction with SEM1


Literature citations

Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood.
Hirsch B.; Shimamura A.; Moreau L.; Baldinger S.; Hag-alshiekh M.; Bostrom B.; Sencer S.; D'Andrea A.D.;
Blood 103:2554-2559(2004)
Cited for: VARIANT FANCD1 PRO-2510;

A comprehensive functional characterization of BRCA2 variants associated with Fanconi anemia using mouse ES cell-based assay.
Biswas K.; Das R.; Alter B.P.; Kuznetsov S.G.; Stauffer S.; North S.L.; Burkett S.; Brody L.C.; Meyer S.; Byrd R.A.; Sharan S.K.;
Blood 118:2430-2442(2011)
Cited for: CHARACTERIZATION OF VARIANTS FANCD1 HIS-2336; PRO-2510 AND CYS-2626; CHARACTERIZATION OF VARIANTS THR-2490 AND ASN-2729; FUNCTION; INTERACTION WITH SEM1;

A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity.
Guidugli L.; Pankratz V.S.; Singh N.; Thompson J.; Erding C.A.; Engel C.; Schmutzler R.; Domchek S.; Nathanson K.; Radice P.; Singer C.; Tonin P.N.; Lindor N.M.; Goldgar D.E.; Couch F.J.;
Cancer Res. 73:265-275(2013)
Cited for: CHARACTERIZATION OF VARIANTS BC PHE-2627; PRO-2653; ARG-2722; GLY-2723; HIS-2723; ASN-2729; HIS-2787; PRO-2792; ARG-2793; ALA-2856; THR-2951; ILE-3013; TRP-3052; GLU-3076; GLU-3095; HIS-3098 AND ILE-3124; CHARACTERIZATION OF VARIANTS ARG-2440; VAL-2466; CYS-2842 AND SER-3063; CHARACTERIZATION OF VARIANT FANCD1 PRO-2510 AND CYS-2626;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.