dbSNP rs2243677: RAD50:c.214-7223T>C (chr5-132568554-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005732.4(RAD50):c.214-7223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,072 control chromosomes in the GnomAD database, including 10,642 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 0.33 ( 10642 hom., cov: 32)

Consequence

RAD50
NM_005732.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.706

Publications

10 publications found

Variant links:

Genes affected

RAD50 (HGNC:9816): (RAD50 double strand break repair protein) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010]

RAD50 Gene-Disease associations (from GenCC):

Nijmegen breakage syndrome-like disorder
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RAD50 links:

ENSG00000283782 (HGNC:):

ENSG00000283782 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4 link	c.214-7223T>C		intron_variant	Intron 2 of 24	ENST00000378823.8	NP_005723.2	Q92878-1A5D6Y3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8 link	c.214-7223T>C		intron_variant	Intron 2 of 24	1	NM_005732.4	ENSP00000368100.4		Q92878-1
ENSG00000283782	ENST00000638452.2 link	c.-84-7223T>C		intron_variant	Intron 4 of 26	5		ENSP00000492349.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49456

AN:

151956

Hom.:

10601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.279

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

GnomAD4 genome

AF:

0.326

AC:

49545

AN:

152072

Hom.:

10642

Cov.:

AF XY:

0.323

AC XY:

24003

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.621

AC:

25773

AN:

41492

American (AMR)

AF:

0.204

AC:

3117

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

837

AN:

3472

East Asian (EAS)

AF:

0.177

AC:

915

AN:

5176

South Asian (SAS)

AF:

0.237

AC:

1141

AN:

4816

European-Finnish (FIN)

AF:

0.231

AC:

2444

AN:

10562

Middle Eastern (MID)

AF:

0.264

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.214

AC:

14547

AN:

67978

Other (OTH)

AF:

0.277

AC:

583

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1416

2831

4247

5662

7078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.309

Hom.:

1164

Bravo

AF:

0.337

Asia WGS

AF:

0.229

AC:

799

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.7

(source)

DANN

Benign

0.86

PhyloP100

-0.71

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over