rs2805834

Variant names:

• chr9-97683584-T-A
• rs2805834
• NM_000380.4:c.673+1339A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000380.4(XPA):​c.673+1339A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,712 control chromosomes in the GnomAD database, including 2,790 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2790 hom., cov: 32)
• Consequence: XPA NM_000380.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 3 publications found

Genes affected

XPA (HGNC:12814): (XPA, DNA damage recognition and repair factor) This gene encodes a zinc finger protein plays a central role in nucleotide excision repair (NER), a specialized type of DNA repair. NER is responsible for repair of UV radiation-induced photoproducts and DNA adducts induced by chemical carcinogens and chemotherapeutic drugs. The encoded protein interacts with DNA and several NER proteins, acting as a scaffold to assemble the NER incision complex at sites of DNA damage. Mutations in this gene cause Xeroderma pigmentosum complementation group A (XP-A), an autosomal recessive skin disorder featuring hypersensitivity to sunlight and increased risk for skin cancer. [provided by RefSeq, Aug 2017]

XPA Gene-Disease associations (from GenCC):

• xeroderma pigmentosum group A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• xeroderma pigmentosum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPA	NM_000380.4	c.673+1339A>T		intron_variant	Intron 5 of 5	ENST00000375128.5	NP_000371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPA	ENST00000375128.5	c.673+1339A>T		intron_variant	Intron 5 of 5	1	NM_000380.4	ENSP00000364270.5
XPA	ENST00000462523.5	n.674-1154A>T		intron_variant	Intron 5 of 6	5		ENSP00000433006.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28479 AN: 151594 Hom.: 2784 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.164

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.188 AC: 28517 AN: 151712 Hom.: 2790 Cov.: 32 AF XY: 0.189 AC XY: 14002 AN XY: 74148

African (AFR) AF: 0.222 AC: 9180 AN: 41364

American (AMR) AF: 0.165 AC: 2515 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 484 AN: 3460

East Asian (EAS) AF: 0.0431 AC: 223 AN: 5180

South Asian (SAS) AF: 0.156 AC: 750 AN: 4812

European-Finnish (FIN) AF: 0.251 AC: 2634 AN: 10486

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12095 AN: 67866

Other (OTH) AF: 0.168 AC: 355 AN: 2110

Alfa AF: 0.181 Hom.: 337

Bravo AF: 0.183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.45
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2805834; hg19: chr9-100445866;