chr2-216128888-C-A

Variant names:

• chr2-216128888-C-A
• rs828704
• NM_021141.4:c.937+1214C>A

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+1214C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,222 control chromosomes in the GnomAD database, including 50,551 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 0.81 (50551 hom., cov: 33)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 21 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 (EAS) allele frequency at 95% confidence interval = 0.863 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+1214C>A		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+1214C>A		intron	N/A	ENSP00000375977.2
	XRCC5	ENST00000460284.5	TSL:1	n.1479+1214C>A		intron	N/A
	XRCC5	ENST00000392133.7	TSL:5	c.937+1214C>A		intron	N/A	ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123839 AN: 152104 Hom.: 50506 Cov.: 33

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.814 AC: 123945 AN: 152222 Hom.: 50551 Cov.: 33 AF XY: 0.815 AC XY: 60673 AN XY: 74436

African (AFR) AF: 0.842 AC: 34965 AN: 41536

American (AMR) AF: 0.827 AC: 12650 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2727 AN: 3472

East Asian (EAS) AF: 0.884 AC: 4584 AN: 5184

South Asian (SAS) AF: 0.766 AC: 3698 AN: 4826

European-Finnish (FIN) AF: 0.842 AC: 8917 AN: 10594

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53924 AN: 68002

Other (OTH) AF: 0.808 AC: 1707 AN: 2112

Alfa AF: 0.797 Hom.: 79588

Bravo AF: 0.818

Asia WGS AF: 0.816 AC: 2842 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	1.2
DANN	Benign	0.35
PhyloP100		0.067
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: rs828704; hg19: chr2-216993611;