chr5-132576155-G-C

Variant names:

• chr5-132576155-G-C
• rs2522414
• NM_005732.4:c.365+227G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005732.4(RAD50):​c.365+227G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,016 control chromosomes in the GnomAD database, including 9,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (9427 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0460
• Publications: 11 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]

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

ENSG00000283782 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-132576155-G-C is Benign according to our data. Variant chr5-132576155-G-C is described in ClinVar as Benign. ClinVar VariationId is 1177683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005732.4. 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
	RAD50	NM_005732.4	MANE Select	c.365+227G>C		intron	N/A	NP_005723.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	ENST00000378823.8	TSL:1 MANE Select	c.365+227G>C		intron	N/A	ENSP00000368100.4	Q92878-1
	ENSG00000283782	ENST00000638452.2	TSL:5	c.68+227G>C		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	RAD50	ENST00000416135.5	TSL:1	c.68+227G>C		intron	N/A	ENSP00000389515.1	C9JNH8

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47338 AN: 151898 Hom.: 9389 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.312 AC: 47426 AN: 152016 Hom.: 9427 Cov.: 32 AF XY: 0.309 AC XY: 22994 AN XY: 74302

African (AFR) AF: 0.574 AC: 23766 AN: 41426

American (AMR) AF: 0.200 AC: 3050 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3472

East Asian (EAS) AF: 0.176 AC: 913 AN: 5180

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4824

European-Finnish (FIN) AF: 0.231 AC: 2440 AN: 10558

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14546 AN: 67972

Other (OTH) AF: 0.269 AC: 569 AN: 2114

Alfa AF: 0.289 Hom.: 917

Bravo AF: 0.320

Asia WGS AF: 0.228 AC: 796 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.71
PhyloP100		0.046
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: rs2522414; hg19: chr5-131911847;