11-64729273-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001098671.2(RASGRP2):c.1592-231C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 152,020 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.019 (41 hom., cov: 32)
• Consequence: RASGRP2 NM_001098671.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.878

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-64729273-G-A is Benign according to our data. Variant chr11-64729273-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1209257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2851/152020) while in subpopulation NFE AF= 0.0278 (1888/67996). AF 95% confidence interval is 0.0267. There are 41 homozygotes in gnomad4. There are 1305 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRP2	NM_001098671.2	c.1592-231C>T		intron_variant		ENST00000394432.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRP2	ENST00000394432.8	c.1592-231C>T		intron_variant		1	NM_001098671.2	P4

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2852 AN: 151926 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00588

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.0751

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00809

Gnomad FIN AF: 0.00693

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0206

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

GnomAD4 genome AF: 0.0188 AC: 2851 AN: 152020 Hom.: 41 Cov.: 32 AF XY: 0.0176 AC XY: 1305 AN XY: 74294

Gnomad4 AFR AF: 0.00589

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.0751

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00791

Gnomad4 FIN AF: 0.00693

Gnomad4 NFE AF: 0.0278

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0197 Hom.: 8

Bravo AF: 0.0199

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	12
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs72927040; hg19: chr11-64496745;