rs2237060

Variant names:

• chr5-132635193-T-G
• rs2237060
• NM_005732.4:c.3390-1922T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005732.4(RAD50):​c.3390-1922T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,158 control chromosomes in the GnomAD database, including 7,919 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 0.29 (7919 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 34 publications found

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]

ENSG00000283782 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4	c.3390-1922T>G		intron_variant	Intron 21 of 24	ENST00000378823.8	NP_005723.2
TH2LCRR	NR_132124.1	n.153+2965A>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.3390-1922T>G		intron_variant	Intron 21 of 24	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000638452.2	c.3093-1922T>G		intron_variant	Intron 23 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43444 AN: 152040 Hom.: 7926 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.285 AC: 43438 AN: 152158 Hom.: 7919 Cov.: 32 AF XY: 0.278 AC XY: 20704 AN XY: 74386

African (AFR) AF: 0.0837 AC: 3479 AN: 41554

American (AMR) AF: 0.317 AC: 4847 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1387 AN: 3466

East Asian (EAS) AF: 0.0630 AC: 327 AN: 5192

South Asian (SAS) AF: 0.230 AC: 1103 AN: 4806

European-Finnish (FIN) AF: 0.299 AC: 3163 AN: 10576

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28110 AN: 67958

Other (OTH) AF: 0.293 AC: 619 AN: 2112

Alfa AF: 0.385 Hom.: 20377

Bravo AF: 0.277

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.73
PhyloP100		-0.42
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: rs2237060; hg19: chr5-131970885;