rs207936

Positions:

• chr2-216175310-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021141.4(XRCC5):​c.1834+13262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 450,836 control chromosomes in the GnomAD database, including 17,439 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 0.24 (5408 hom., cov: 32)
  • Exomes 𝑓: 0.27 (12031 hom.)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC5	NM_021141.4	c.1834+13262C>T		intron_variant		ENST00000392132.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC5	ENST00000392132.7	c.1834+13262C>T		intron_variant		1	NM_021141.4	P1
	ENST00000441511.2	n.723G>A		non_coding_transcript_exon_variant	1/1
XRCC5	ENST00000460284.5	n.2376+13262C>T		intron_variant, non_coding_transcript_variant		1
XRCC5	ENST00000392133.7	c.1834+13262C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36390 AN: 152010 Hom.: 5405 Cov.: 32

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.266 AC: 79517 AN: 298708 Hom.: 12031 Cov.: 0 AF XY: 0.264 AC XY: 45205 AN XY: 171518

Gnomad4 AFR exome AF: 0.0768

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.239 AC: 36390 AN: 152128 Hom.: 5408 Cov.: 32 AF XY: 0.234 AC XY: 17395 AN XY: 74364

Gnomad4 AFR AF: 0.0868

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0521

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.246

Alfa AF: 0.303 Hom.: 1787

Bravo AF: 0.224

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs207936; hg19: chr2-217040033;