2-216146098-C-A

Position:

• chr2-216146098-C-A

Variant summary

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

The NM_021141.4(XRCC5):​c.1477-1985C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,078 control chromosomes in the GnomAD database, including 2,397 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 0.16 (2397 hom., cov: 32)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.1477-1985C>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.1477-1985C>A		intron_variant		1	NM_021141.4	ENSP00000375977	P1
XRCC5	ENST00000460284.5	n.2019-1985C>A		intron_variant, non_coding_transcript_variant		1
XRCC5	ENST00000392133.7	c.1477-1985C>A		intron_variant		5		ENSP00000375978	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24345 AN: 151960 Hom.: 2392 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.160 AC: 24346 AN: 152078 Hom.: 2397 Cov.: 32 AF XY: 0.164 AC XY: 12156 AN XY: 74320

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.174

Alfa AF: 0.200 Hom.: 3550

Bravo AF: 0.151

Asia WGS AF: 0.171 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.77

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: rs16855458; hg19: chr2-217010821;