rs2440

Variant names:

• chr2-216206043-G-A
• rs2440
• NM_021141.4:c.*841G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-216206043-G-A
• chr2-216206043-G-C
• chr2-216206043-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021141.4(XRCC5):​c.*841G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,052 control chromosomes in the GnomAD database, including 10,916 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 0.36 (10916 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: XRCC5 NM_021141.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 28 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.*841G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.*841G>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000392133.7	c.*841G>A		3_prime_UTR_variant	Exon 23 of 23	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54899 AN: 151934 Hom.: 10912 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.412

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.361 AC: 54905 AN: 152052 Hom.: 10916 Cov.: 32 AF XY: 0.369 AC XY: 27432 AN XY: 74316

African (AFR) AF: 0.215 AC: 8912 AN: 41492

American (AMR) AF: 0.535 AC: 8167 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1454 AN: 3470

East Asian (EAS) AF: 0.724 AC: 3750 AN: 5176

South Asian (SAS) AF: 0.331 AC: 1597 AN: 4818

European-Finnish (FIN) AF: 0.428 AC: 4519 AN: 10560

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25206 AN: 67948

Other (OTH) AF: 0.413 AC: 870 AN: 2106

Alfa AF: 0.371 Hom.: 6212

Bravo AF: 0.370

Asia WGS AF: 0.481 AC: 1672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.73
DANN	Benign	0.61
PhyloP100		-0.21
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: rs2440; hg19: chr2-217070766;