chr11-64727506-AT-A

Position:

• chr11-64727506-AT-A

Variant summary

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

The NM_001098671.2(RASGRP2):​c.1772-147delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 240,620 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (660 hom., cov: 0)
  • Exomes 𝑓: 0.19 (16 hom.)
  • Failed GnomAD Quality Control
• Consequence: RASGRP2 NM_001098671.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

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]

RASGRP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-64727506-AT-A is Benign according to our data. Variant chr11-64727506-AT-A is described in ClinVar as [Benign]. Clinvar id is 1226530.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRP2	NM_001098671.2	c.1772-147delA		intron_variant		ENST00000394432.8	NP_001092141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRP2	ENST00000394432.8	c.1772-147delA		intron_variant		1	NM_001098671.2	ENSP00000377953.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 14680 AN: 75214 Hom.: 662 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.191 AC: 45904 AN: 240620 Hom.: 16 AF XY: 0.191 AC XY: 24993 AN XY: 130788

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.195 AC: 14681 AN: 75228 Hom.: 660 Cov.: 0 AF XY: 0.192 AC XY: 6627 AN XY: 34470

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.214

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;