2-216173745-T-C

Variant names:

• chr2-216173745-T-C
• rs207932
• NM_021141.4:c.1834+11697T>C

Variant summary

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

The NM_021141.4(XRCC5):​c.1834+11697T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,972 control chromosomes in the GnomAD database, including 27,456 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 0.59 (27456 hom., cov: 31)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.1834+11697T>C		intron_variant	Intron 16 of 20	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.1834+11697T>C		intron_variant	Intron 16 of 20	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.2376+11697T>C		intron_variant	Intron 13 of 17	1
XRCC5	ENST00000392133.7	c.1834+11697T>C		intron_variant	Intron 18 of 22	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90317 AN: 151854 Hom.: 27418 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.595 AC: 90403 AN: 151972 Hom.: 27456 Cov.: 31 AF XY: 0.589 AC XY: 43720 AN XY: 74270

African (AFR) AF: 0.695 AC: 28787 AN: 41434

American (AMR) AF: 0.434 AC: 6628 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1927 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1619 AN: 5170

South Asian (SAS) AF: 0.666 AC: 3212 AN: 4820

European-Finnish (FIN) AF: 0.563 AC: 5933 AN: 10536

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.597 AC: 40560 AN: 67966

Other (OTH) AF: 0.540 AC: 1140 AN: 2112

Alfa AF: 0.590 Hom.: 37674

Bravo AF: 0.582

Asia WGS AF: 0.523 AC: 1819 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.82
PhyloP100		-0.55
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: rs207932; hg19: chr2-217038468; COSMIC: COSV107495098; COSMIC: COSV107495098;