rs9288518

Variant names:

• chr2-216196997-A-G
• rs9288518
• NM_021141.4:c.2109+2011A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-216196997-A-G
• chr2-216196997-A-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.2109+2011A>G variant causes a intron 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 10,946 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 (10946 hom., cov: 31)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• Publications: 12 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=-0.85).
• 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.2109+2011A>G		intron_variant	Intron 19 of 20	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.2109+2011A>G		intron_variant	Intron 19 of 20	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.2651+2011A>G		intron_variant	Intron 16 of 17	1
XRCC5	ENST00000392133.7	c.2109+2011A>G		intron_variant	Intron 21 of 22	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54938 AN: 151936 Hom.: 10942 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.361 AC: 54942 AN: 152052 Hom.: 10946 Cov.: 31 AF XY: 0.369 AC XY: 27449 AN XY: 74296

African (AFR) AF: 0.214 AC: 8883 AN: 41498

American (AMR) AF: 0.535 AC: 8176 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3466

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

South Asian (SAS) AF: 0.333 AC: 1604 AN: 4816

European-Finnish (FIN) AF: 0.429 AC: 4516 AN: 10530

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.372 AC: 25259 AN: 67974

Other (OTH) AF: 0.414 AC: 874 AN: 2110

Alfa AF: 0.379 Hom.: 36346

Bravo AF: 0.370

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9288518; hg19: chr2-217061720;