2-216180336-C-T

Variant names:

• chr2-216180336-C-T
• rs3770502
• NM_021141.4:c.1835-9889C>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.1835-9889C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,114 control chromosomes in the GnomAD database, including 1,314 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 0.12 (1314 hom., cov: 31)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 9 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 (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.1835-9889C>T		intron_variant	Intron 16 of 20	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.1835-9889C>T		intron_variant	Intron 16 of 20	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.2377-9889C>T		intron_variant	Intron 13 of 17	1
XRCC5	ENST00000392133.7	c.1835-9889C>T		intron_variant	Intron 18 of 22	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18630 AN: 151996 Hom.: 1315 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.123 AC: 18645 AN: 152114 Hom.: 1314 Cov.: 31 AF XY: 0.123 AC XY: 9158 AN XY: 74366

African (AFR) AF: 0.146 AC: 6047 AN: 41520

American (AMR) AF: 0.0848 AC: 1296 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 414 AN: 3458

East Asian (EAS) AF: 0.149 AC: 770 AN: 5166

South Asian (SAS) AF: 0.277 AC: 1333 AN: 4816

European-Finnish (FIN) AF: 0.120 AC: 1267 AN: 10584

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7110 AN: 67982

Other (OTH) AF: 0.110 AC: 232 AN: 2106

Alfa AF: 0.0996 Hom.: 1206

Bravo AF: 0.116

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.55
PhyloP100		-0.39
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: rs3770502; hg19: chr2-217045059;