NM_000380.4(XPA):c.731A>G (p.His244Arg) AND Xeroderma pigmentosum group A

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Mar 20, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000668335.10

Allele description [Variation Report for NM_000380.4(XPA):c.731A>G (p.His244Arg)]

NM_000380.4(XPA):c.731A>G (p.His244Arg)

Gene:

XPA:XPA, DNA damage recognition and repair factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.33

Genomic location:

Preferred name:

NM_000380.4(XPA):c.731A>G (p.His244Arg)

HGVS:

NC_000009.12:g.97675530T>C
NG_011642.1:g.26880A>G
NM_000380.4:c.731A>GMANE SELECT
NM_001354975.2:c.605A>G
NP_000371.1:p.His244Arg
NP_000371.1:p.His244Arg
NP_001341904.1:p.His202Arg
LRG_471t1:c.731A>G
LRG_471:g.26880A>G
LRG_471p1:p.His244Arg
NC_000009.11:g.100437812T>C
NM_000380.3:c.731A>G
NR_027302.2:n.1010A>G
NR_149091.2:n.507A>G
NR_149092.2:n.673A>G
NR_149093.2:n.1199A>G
NR_149094.2:n.1093A>G
P23025:p.His244Arg

Protein change:

H202R

Links:

UniProtKB: P23025#VAR_007731; dbSNP: rs144725456

NCBI 1000 Genomes Browser:

rs144725456

Molecular consequence:

NM_000380.4:c.731A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354975.2:c.605A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_027302.2:n.1010A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149091.2:n.507A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149092.2:n.673A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149093.2:n.1199A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149094.2:n.1093A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Xeroderma pigmentosum group A (XPA)
Synonyms:: Xeroderma pigmentosum, type 1; Xeroderma pigmentosum, complementation group A; XP, group A
Identifiers:: MONDO: MONDO:0010210; MedGen: C0268135; Orphanet: 910; OMIM: 278700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000475591	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9753735, 1372103 Citation Link,
SCV000792915	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Aug 3, 2017)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 1372103, 9753735 Citation Link,
SCV004206940	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 20, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000475591

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000792915

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Aug 3, 2017)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV004206940

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 20, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Identification of splicing mutations of the last nucleotides of exons, a nonsense mutation, and a missense mutation of the XPAC gene as causes of group A xeroderma pigmentosum.

Satokata I, Tanaka K, Yuba S, Okada Y.

Mutat Res. 1992 Mar;273(2):203-12.

PubMed [citation]

PMID:: 1372103

Mutational analysis of a function of xeroderma pigmentosum group A (XPA) protein in strand-specific DNA repair.

Kobayashi T, Takeuchi S, Saijo M, Nakatsu Y, Morioka H, Otsuka E, Wakasugi M, Nikaido O, Tanaka K.

Nucleic Acids Res. 1998 Oct 15;26(20):4662-8.

PubMed [citation]

PMID:: 9753735
PMCID:: PMC147903

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000475591.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The XPA c.731A>G (p.His244Arg) variant is a missense variant that has been reported in at least one study, in which it was found in a compound heterozygous state in one individual with xeroderma pigmentosum (Satokata et al. 1992). Control data are unavailable for this variant, which is reported at a frequency of 0.00045 in the European (Finnish) population of the Exome Aggregation Consortium. In vitro studies using patient-derived cell lines found the p.His244Arg variant to have reduced ultraviolet resistance while maintaining expression levels similar to wildtype (Satokata et al. 1992; Kobayashi et al. 1998). The evidence for this variant is limited. Therefore, the p.His244Arg variant is classified as a variant of unknown significance but suspicious for xeroderma pigmentosum. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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 Counsyl, SCV000792915.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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

From Baylor Genetics, SCV004206940.2

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

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

Last Updated: Jun 17, 2024

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