chr2-216112600-G-A

Variant names:

• chr2-216112600-G-A
• rs828911
• NM_021141.4:c.22-416G>A

Variant summary

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

The NM_021141.4(XRCC5):​c.22-416G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,122 control chromosomes in the GnomAD database, including 11,601 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 0.37 (11601 hom., cov: 33)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 10 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 (SAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021141.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	NM_021141.4	MANE Select	c.22-416G>A		intron	N/A	NP_066964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	ENST00000392132.7	TSL:1 MANE Select	c.22-416G>A		intron	N/A	ENSP00000375977.2
	XRCC5	ENST00000392133.7	TSL:5	c.22-416G>A		intron	N/A	ENSP00000375978.3
	XRCC5	ENST00000417391.1	TSL:3	c.-18-416G>A		intron	N/A	ENSP00000401318.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56563 AN: 152006 Hom.: 11590 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.372 AC: 56584 AN: 152122 Hom.: 11601 Cov.: 33 AF XY: 0.371 AC XY: 27606 AN XY: 74340

African (AFR) AF: 0.222 AC: 9203 AN: 41514

American (AMR) AF: 0.291 AC: 4446 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1556 AN: 3472

East Asian (EAS) AF: 0.210 AC: 1090 AN: 5180

South Asian (SAS) AF: 0.525 AC: 2526 AN: 4816

European-Finnish (FIN) AF: 0.456 AC: 4801 AN: 10532

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31817 AN: 67998

Other (OTH) AF: 0.389 AC: 822 AN: 2114

Alfa AF: 0.324 Hom.: 1315

Bravo AF: 0.348

Asia WGS AF: 0.394 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.47
PhyloP100		-0.040
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: rs828911; hg19: chr2-216977323;