rs828702

Variant names:

• chr2-216128755-A-G
• rs828702
• NM_021141.4:c.937+1081A>G

Variant summary

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

The NM_021141.4(XRCC5):​c.937+1081A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,004 control chromosomes in the GnomAD database, including 20,875 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 0.52 (20875 hom., cov: 32)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487
• Publications: 4 publications found

Genes affected

XRCC5 (HGNC:12833): (X-ray repair cross complementing 5) The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021141.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	NM_021141.4	MANE Select	c.937+1081A>G		intron	N/A	NP_066964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	ENST00000392132.7	TSL:1 MANE Select	c.937+1081A>G		intron	N/A	ENSP00000375977.2
	XRCC5	ENST00000460284.5	TSL:1	n.1479+1081A>G		intron	N/A
	XRCC5	ENST00000392133.7	TSL:5	c.937+1081A>G		intron	N/A	ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78711 AN: 151886 Hom.: 20841 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.518 AC: 78783 AN: 152004 Hom.: 20875 Cov.: 32 AF XY: 0.511 AC XY: 37982 AN XY: 74272

African (AFR) AF: 0.539 AC: 22322 AN: 41428

American (AMR) AF: 0.386 AC: 5892 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1690 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1094 AN: 5160

South Asian (SAS) AF: 0.539 AC: 2594 AN: 4812

European-Finnish (FIN) AF: 0.544 AC: 5752 AN: 10564

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.558 AC: 37925 AN: 67976

Other (OTH) AF: 0.496 AC: 1048 AN: 2114

Alfa AF: 0.546 Hom.: 2835

Bravo AF: 0.503

Asia WGS AF: 0.421 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.93
DANN	Benign	0.38
PhyloP100		-0.49
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: rs828702; hg19: chr2-216993478;