UniProtKB/Swiss-Prot P49005: Variant p.Asp293Asn

DNA polymerase delta subunit 2
Gene: POLD2
Feedback?

Variant information Variant position:

293 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Aspartate (D) to Asparagine (N) at position 293 (D293N, p.Asp293Asn). 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:

Change from medium size and acidic (D) to medium size and polar (N) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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
Variant description:

Found in a patient with a syndromic combined immunodeficiency disorder; uncertain significance; affects protein stability; strongly reduced interaction with POLD1 and POLD3; in peripheral blood mononuclear cells, after anti-CD3 and anti-CD28 stimulation, drastically reduced protein expression levels, despite transcript levels similar to that of wild-type controls; patient's cells also show strongly decreased POLD1 and POLD3 protein levels; no effect on DNA prolymerase activity, when tested in transfected HEK293 cells. Any additional useful information about the variant.

Sequence information Variant position:

293 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

469 The length of the canonical sequence.
Location on the sequence:

VEAVKMLDEILLQLSASVPV D VMPGEFDPTNYTLPQQPLHP 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                         VEAVKMLDEILLQLSASV---PVDVMPGEFDPTNYTLPQQPLHP

Mouse                         VEAVKMLDEILLQLSASV---PVDVMPGEFDPTNYTLPQQP

Rat                           VEAVKMLDEILLQLSASV---PVDVMPGEFDPTNYTLPQQP

Bovine                        VEAVKMLDEILLQLSASV---PVDVMPGEFDPTNYTLPQQP

Xenopus laevis                VEAVKMLDEILLQMSGSV---SVDVMPGAFDPTNYILPQQP

Caenorhabditis elegans        TASLITVDKIINSIAEKPLVNTVDVTPGVGDPCSSMWPLPP

Drosophila                    VQAVSQLDQWFASWARSL---PVDIMPGPYDPANFMLPQQP

Baker's yeast                 MISLTEFSKFLHNILPSI---SVDIMPGTNDPSDKSLPQQP

Fission yeast                 PNPTFQLDNFLDQVCSSI---DVTLMPGPYDYSSTILPQQP

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.

Type	Positions	Description
Chain	1 – 469	DNA polymerase delta subunit 2
Beta strand	292 – 295

Literature citations
Polymerase delta deficiency causes syndromic immunodeficiency with replicative stress.
Conde C.D.; Petronczki O.Y.; Baris S.; Willmann K.L.; Girardi E.; Salzer E.; Weitzer S.; Ardy R.C.; Krolo A.; Ijspeert H.; Kiykim A.; Karakoc-Aydiner E.; Foerster-Waldl E.; Kager L.; Pickl W.F.; Superti-Furga G.; Martinez J.; Loizou J.I.; Ozen A.; van der Burg M.; Boztug K.;
J. Clin. Invest. 129:4194-4206(2019)
Cited for: VARIANT ASN-293; CHARACTERIZATION OF VARIANT ASN-293; INTERACTION WITH POLD1 AND POLD3;

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.