chr2-216123238-A-C

Variant names:

• chr2-216123238-A-C
• rs828699
• NM_021141.4:c.683+985A>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.683+985A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,944 control chromosomes in the GnomAD database, including 20,866 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 0.52 (20866 hom., cov: 32)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 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.683+985A>C		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.683+985A>C		intron	N/A	ENSP00000375977.2
	XRCC5	ENST00000460284.5	TSL:1	n.1225+985A>C		intron	N/A
	XRCC5	ENST00000392133.7	TSL:5	c.683+985A>C		intron	N/A	ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78694 AN: 151826 Hom.: 20832 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.518 AC: 78766 AN: 151944 Hom.: 20866 Cov.: 32 AF XY: 0.511 AC XY: 37988 AN XY: 74272

African (AFR) AF: 0.540 AC: 22333 AN: 41394

American (AMR) AF: 0.386 AC: 5889 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1689 AN: 3472

East Asian (EAS) AF: 0.214 AC: 1108 AN: 5168

South Asian (SAS) AF: 0.539 AC: 2599 AN: 4824

European-Finnish (FIN) AF: 0.543 AC: 5729 AN: 10558

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37903 AN: 67938

Other (OTH) AF: 0.496 AC: 1049 AN: 2116

Alfa AF: 0.530 Hom.: 9861

Bravo AF: 0.504

Asia WGS AF: 0.421 AC: 1464 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.5
DANN	Benign	0.42
PhyloP100		-0.75
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: rs828699; hg19: chr2-216987961;