chr2-216193123-G-A

Position:

• chr2-216193123-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021141.4(XRCC5):​c.2041+388G>A 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 151,996 control chromosomes in the GnomAD database, including 41,363 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 (41363 hom., cov: 31)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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/exons	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.2041+388G>A		intron_variant		ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.2041+388G>A		intron_variant		1	NM_021141.4	ENSP00000375977	P1
XRCC5	ENST00000460284.5	n.2583+388G>A		intron_variant, non_coding_transcript_variant		1
XRCC5	ENST00000392133.7	c.2041+388G>A		intron_variant		5		ENSP00000375978	P1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109941 AN: 151878 Hom.: 41297 Cov.: 31

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: 0.662

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.724 AC: 110065 AN: 151996 Hom.: 41363 Cov.: 31 AF XY: 0.731 AC XY: 54297 AN XY: 74308

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.717

Alfa AF: 0.642 Hom.: 14671

Bravo AF: 0.740

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	-0.94
CADD	Benign	0.26
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs3821104; hg19: chr2-217057846;