NM_000107.3(DDB2):c.818G>A (p.Arg273His) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003555986.8

Allele description [Variation Report for NM_000107.3(DDB2):c.818G>A (p.Arg273His)]

NM_000107.3(DDB2):c.818G>A (p.Arg273His)

Gene:

DDB2:damage specific DNA binding protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p11.2

Genomic location:

Preferred name:

NM_000107.3(DDB2):c.818G>A (p.Arg273His)

HGVS:

NC_000011.10:g.47234872G>A
NG_009365.1:g.24931G>A
NM_000107.3:c.818G>AMANE SELECT
NM_001300734.2:c.457-2965G>A
NP_000098.1:p.Arg273His
LRG_467:g.24931G>A
NC_000011.9:g.47256423G>A
Q92466:p.Arg273His

Protein change:

R273H; ARG273HIS

Links:

UniProtKB: Q92466#VAR_010142; OMIM: 600811.0002; dbSNP: rs121434640

NCBI 1000 Genomes Browser:

rs121434640

Molecular consequence:

NM_001300734.2:c.457-2965G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000107.3:c.818G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004294777	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 22, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8798680, 21107348, 10777490, 16964240, 28492532
SCV005042489	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Apr 1, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004294777

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 22, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV005042489

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely pathogenic
(Apr 1, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype.

Nichols AF, Ong P, Linn S.

J Biol Chem. 1996 Oct 4;271(40):24317-20.

PubMed [citation]

PMID:: 8798680

Multiple skin cancers in adults with mutations in the XP-E (DDB2) DNA repair gene.

Oh KS, Emmert S, Tamura D, DiGiovanna JJ, Kraemer KH.

J Invest Dermatol. 2011 Mar;131(3):785-8. doi: 10.1038/jid.2010.352. Epub 2010 Nov 25. No abstract available.

PubMed [citation]

PMID:: 21107348
PMCID:: PMC3471370

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004294777.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 273 of the DDB2 protein (p.Arg273His). This variant is present in population databases (rs121434640, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of xeroderma pigmentosum (PMID: 8798680, 21107348; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 8788). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects DDB2 function (PMID: 10777490, 16964240). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV005042489.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

DDB2: PS3, PM2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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