2-216193467-T-C

Variant names:

• chr2-216193467-T-C
• rs3770492
• NM_021141.4:c.2041+732T>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.2041+732T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,184 control chromosomes in the GnomAD database, including 41,415 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 0.72 (41415 hom., cov: 33)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.2041+732T>C		intron_variant	Intron 18 of 20	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.2041+732T>C		intron_variant	Intron 18 of 20	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.2583+732T>C		intron_variant	Intron 15 of 17	1
XRCC5	ENST00000392133.7	c.2041+732T>C		intron_variant	Intron 20 of 22	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110075 AN: 152066 Hom.: 41349 Cov.: 33

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.724 AC: 110199 AN: 152184 Hom.: 41415 Cov.: 33 AF XY: 0.731 AC XY: 54360 AN XY: 74398

African (AFR) AF: 0.905 AC: 37589 AN: 41514

American (AMR) AF: 0.763 AC: 11668 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3472

East Asian (EAS) AF: 0.946 AC: 4914 AN: 5192

South Asian (SAS) AF: 0.783 AC: 3779 AN: 4828

European-Finnish (FIN) AF: 0.661 AC: 7001 AN: 10586

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40691 AN: 67982

Other (OTH) AF: 0.717 AC: 1516 AN: 2114

Alfa AF: 0.522 Hom.: 1371

Bravo AF: 0.741

Asia WGS AF: 0.846 AC: 2943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.4
DANN	Benign	0.73
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3770492; hg19: chr2-217058190;