2-216138429-T-C

Position:

• chr2-216138429-T-C

Variant summary

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

The NM_021141.4(XRCC5):​c.1342+250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,148 control chromosomes in the GnomAD database, including 12,423 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 0.39 (12423 hom., cov: 32)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.984

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]

XRCC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.1342+250T>C		intron_variant		ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.1342+250T>C		intron_variant		1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.1884+250T>C		intron_variant		1
XRCC5	ENST00000392133.7	c.1342+250T>C		intron_variant		5		ENSP00000375978.3
XRCC5	ENST00000471649.1	n.476+250T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58775 AN: 152030 Hom.: 12407 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.386 AC: 58792 AN: 152148 Hom.: 12423 Cov.: 32 AF XY: 0.393 AC XY: 29220 AN XY: 74384

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.434

Alfa AF: 0.405 Hom.: 17065

Bravo AF: 0.389

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2303400; hg19: chr2-217003152;