2-216138429-T-C

Variant names:

• chr2-216138429-T-C
• rs2303400
• NM_021141.4:c.1342+250T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.82).
• 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 rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.1342+250T>C		intron_variant	Intron 12 of 20	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.1342+250T>C		intron_variant	Intron 12 of 20	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.1884+250T>C		intron_variant	Intron 9 of 17	1
XRCC5	ENST00000392133.7	c.1342+250T>C		intron_variant	Intron 14 of 22	5		ENSP00000375978.3
XRCC5	ENST00000471649.1	n.476+250T>C		intron_variant	Intron 5 of 5	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

African (AFR) AF: 0.238 AC: 9890 AN: 41476

American (AMR) AF: 0.539 AC: 8245 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1523 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3480 AN: 5184

South Asian (SAS) AF: 0.333 AC: 1611 AN: 4832

European-Finnish (FIN) AF: 0.516 AC: 5460 AN: 10574

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27122 AN: 67998

Other (OTH) AF: 0.434 AC: 917 AN: 2114

Alfa AF: 0.404 Hom.: 21438

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
PhyloP100		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2303400; hg19: chr2-217003152;