11-64727506-ATT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001098671.2(RASGRP2):c.1772-148_1772-147del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 246,780 control chromosomes in the GnomAD database, including 208 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (7585 hom., cov: 0)
  • Exomes 𝑓: 0.35 (208 hom.)
  • Failed GnomAD Quality Control
• Consequence: RASGRP2 NM_001098671.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.227

Genes affected

RASGRP2 (HGNC:9879): (RAS guanyl releasing protein 2) The protein encoded by this gene is a brain-enriched nucleotide exchanged factor that contains an N-terminal GEF domain, 2 tandem repeats of EF-hand calcium-binding motifs, and a C-terminal diacylglycerol/phorbol ester-binding domain. This protein can activate small GTPases, including RAS and RAP1/RAS3. The nucleotide exchange activity of this protein can be stimulated by calcium and diacylglycerol. Four alternatively spliced transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-64727506-ATT-A is Benign according to our data. Variant chr11-64727506-ATT-A is described in ClinVar as [Benign]. Clinvar id is 1286700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRP2	NM_001098671.2	c.1772-148_1772-147del		intron_variant		ENST00000394432.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRP2	ENST00000394432.8	c.1772-148_1772-147del		intron_variant		1	NM_001098671.2	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 38426 AN: 76244 Hom.: 7594 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.348 AC: 85871 AN: 246780 Hom.: 208 AF XY: 0.348 AC XY: 46772 AN XY: 134226

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.504 AC: 38417 AN: 76256 Hom.: 7585 Cov.: 0 AF XY: 0.504 AC XY: 17581 AN XY: 34910

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.497

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34854951; hg19: chr11-64494978;