Variant rs2074369 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005732.4(RAD50):c.3476-110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,229,542 control chromosomes in the GnomAD database, including 39,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 10444 hom., cov: 32)

Exomes 𝑓: 0.22 ( 28922 hom. )

Consequence

RAD50
NM_005732.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.327

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 links:

TH2LCRR (HGNC:40495): (T helper type 2 locus control region associated RNA)

TH2LCRR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 5-132637971-T-C is Benign according to our data. Variant chr5-132637971-T-C is described in ClinVar as [Benign]. Clinvar id is 1180917.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD50	NM_005732.4 linkuse as main transcript	c.3476-110T>C		intron_variant		ENST00000378823.8	NP_005723.2
TH2LCRR	NR_132124.1 linkuse as main transcript	n.153+187A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8 linkuse as main transcript	c.3476-110T>C		intron_variant		1	NM_005732.4	ENSP00000368100	P1	Q92878-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49490

AN:

151962

Hom.:

10405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.607

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.285

GnomAD4 exome

AF:

0.220

AC:

237494

AN:

1077462

Hom.:

28922

AF XY:

0.222

AC XY:

121883

AN XY:

550256

show subpopulations

Gnomad4 AFR exome

AF:

0.613

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.326

AC:

49577

AN:

152080

Hom.:

10444

Cov.:

AF XY:

0.323

AC XY:

24041

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.607

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.178

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.244

Gnomad4 NFE

AF:

0.220

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.298

Hom.:

2109

Bravo

AF:

0.335

Asia WGS

AF:

0.230

AC:

803

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

5.6

DANN

Benign

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over