11-64727506-ATTTTTTTTTTTTTT-ATTTTTTTTTTT

Variant names:

• chr11-64727506-ATTT-A
• rs34854951
• NM_001098671.2:c.1772-149_1772-147delAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001098671.2(RASGRP2):​c.1772-149_1772-147delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 240,182 control chromosomes in the GnomAD database, including 7 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0059 (2 hom., cov: 0)
  • Exomes 𝑓: 0.20 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: RASGRP2 NM_001098671.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRP2	NM_001098671.2	c.1772-149_1772-147delAAA		intron_variant	Intron 15 of 16	ENST00000394432.8	NP_001092141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRP2	ENST00000394432.8	c.1772-149_1772-147delAAA		intron_variant	Intron 15 of 16	1	NM_001098671.2	ENSP00000377953.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 445 AN: 74962 Hom.: 2 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00459

Gnomad AMI AF: 0.0116

Gnomad AMR AF: 0.00972

Gnomad ASJ AF: 0.00154

Gnomad EAS AF: 0.00306

Gnomad SAS AF: 0.00334

Gnomad FIN AF: 0.00714

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00646

Gnomad OTH AF: 0.00846

GnomAD4 exome AF: 0.204 AC: 48945 AN: 240182 Hom.: 7 AF XY: 0.203 AC XY: 26538 AN XY: 130468

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00595 AC: 446 AN: 74976 Hom.: 2 Cov.: 0 AF XY: 0.00640 AC XY: 220 AN XY: 34358

Gnomad4 AFR AF: 0.00463

Gnomad4 AMR AF: 0.00971

Gnomad4 ASJ AF: 0.00154

Gnomad4 EAS AF: 0.00307

Gnomad4 SAS AF: 0.00336

Gnomad4 FIN AF: 0.00714

Gnomad4 NFE AF: 0.00646

Gnomad4 OTH AF: 0.00839

ClinVar

Not reported in ClinVar

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;