chr11-64727506-A-AT

Variant names:

• chr11-64727506-A-AT
• rs34854951
• NM_001098671.2:c.1772-147dupA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001098671.2(RASGRP2):​c.1772-147dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 247,574 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0098 (10 hom., cov: 0)
  • Exomes 𝑓: 0.0046 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RASGRP2 NM_001098671.2 intron
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Variant has high frequency in the AFR(0.0291059) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00459 (1137/247574) while in subpopulation AFR AF= 0.0317 (189/5956). AF 95% confidence interval is 0.028. There are 0 homozygotes in gnomad4_exome. There are 592 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRP2	NM_001098671.2	c.1772-147dupA		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.1772-147_1772-146insA		intron_variant	Intron 15 of 16	1	NM_001098671.2	ENSP00000377953.3

Frequencies

GnomAD3 genomes AF: 0.00981 AC: 735 AN: 74936 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00345

Gnomad ASJ AF: 0.00411

Gnomad EAS AF: 0.000383

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000386

Gnomad OTH AF: 0.00530

GnomAD4 exome AF: 0.00459 AC: 1137 AN: 247574 Hom.: 0 AF XY: 0.00440 AC XY: 592 AN XY: 134624

Gnomad4 AFR exome AF: 0.0317

Gnomad4 AMR exome AF: 0.00665

Gnomad4 ASJ exome AF: 0.00260

Gnomad4 EAS exome AF: 0.00549

Gnomad4 SAS exome AF: 0.00269

Gnomad4 FIN exome AF: 0.00384

Gnomad4 NFE exome AF: 0.00383

Gnomad4 OTH exome AF: 0.00504

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00979 AC: 734 AN: 74950 Hom.: 10 Cov.: 0 AF XY: 0.00998 AC XY: 343 AN XY: 34358

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.00345

Gnomad4 ASJ AF: 0.00411

Gnomad4 EAS AF: 0.000384

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000387

Gnomad4 OTH AF: 0.00525

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;