Genetic Variant NM_021141.4:c.1834+13262C>T (chr2-216175310-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_021141.4(XRCC5):c.1834+13262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 450,836 control chromosomes in the GnomAD database, including 17,439 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 0.24 ( 5408 hom., cov: 32)

Exomes 𝑓: 0.27 ( 12031 hom. )

Consequence

XRCC5
NM_021141.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

Publications

4 publications found

Variant links:

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]

XRCC5 links:

ENSG00000236478 (HGNC:):

ENSG00000236478 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	NM_021141.4	MANE Select	c.1834+13262C>T		intron	N/A	NP_066964.1	P13010

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XRCC5	ENST00000392132.7	TSL:1 MANE Select	c.1834+13262C>T	intron	N/A	ENSP00000375977.2	P13010
XRCC5	ENST00000460284.5	TSL:1	n.2376+13262C>T	intron	N/A
XRCC5	ENST00000947464.1		c.1900+2108C>T	intron	N/A	ENSP00000617523.1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36390

AN:

152010

Hom.:

5405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0868

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.0522

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.266

AC:

79517

AN:

298708

Hom.:

12031

Cov.:

AF XY:

0.264

AC XY:

45205

AN XY:

171518

show subpopulations

African (AFR)

AF:

0.0768

AC:

610

AN:

7944

American (AMR)

AF:

0.158

AC:

3869

AN:

24556

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

2048

AN:

6994

East Asian (EAS)

AF:

0.0500

AC:

621

AN:

12426

South Asian (SAS)

AF:

0.200

AC:

10792

AN:

53946

European-Finnish (FIN)

AF:

0.272

AC:

4312

AN:

15852

Middle Eastern (MID)

AF:

0.226

AC:

234

AN:

1034

European-Non Finnish (NFE)

AF:

0.328

AC:

53264

AN:

162272

Other (OTH)

AF:

0.275

AC:

3767

AN:

13684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

2131

4262

6394

8525

10656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.239

AC:

36390

AN:

152128

Hom.:

5408

Cov.:

AF XY:

0.234

AC XY:

17395

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0868

AC:

3603

AN:

41530

American (AMR)

AF:

0.206

AC:

3150

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1030

AN:

3470

East Asian (EAS)

AF:

0.0521

AC:

270

AN:

5182

South Asian (SAS)

AF:

0.196

AC:

946

AN:

4820

European-Finnish (FIN)

AF:

0.309

AC:

3264

AN:

10558

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.344

AC:

23368

AN:

67974

Other (OTH)

AF:

0.246

AC:

518

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1338

2676

4015

5353

6691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.300

Hom.:

2817

Bravo

AF:

0.224

Asia WGS

AF:

0.145

AC:

502

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over