11-64727506-ATTTTTTTTTTTTTT-ATTTTTTTT

Variant names:

• chr11-64727506-ATTTTTT-A
• rs34854951
• NM_001098671.2:c.1772-152_1772-147delAAAAAA

Variant summary

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

The NM_001098671.2(RASGRP2):​c.1772-152_1772-147delAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 321,348 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 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0045 (0 hom.)
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00451 (1111/246384) while in subpopulation AFR AF= 0.00869 (52/5984). AF 95% confidence interval is 0.00681. There are 0 homozygotes in gnomad4_exome. There are 583 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.1772-152_1772-147delAAAAAA		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.1772-152_1772-147delAAAAAA		intron_variant	Intron 15 of 16	1	NM_001098671.2	ENSP00000377953.3

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 1 AN: 74964 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000420

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00451 AC: 1111 AN: 246384 Hom.: 0 AF XY: 0.00435 AC XY: 583 AN XY: 133908

Gnomad4 AFR exome AF: 0.00869

Gnomad4 AMR exome AF: 0.00478

Gnomad4 ASJ exome AF: 0.00384

Gnomad4 EAS exome AF: 0.00485

Gnomad4 SAS exome AF: 0.00306

Gnomad4 FIN exome AF: 0.00420

Gnomad4 NFE exome AF: 0.00470

Gnomad4 OTH exome AF: 0.00443

GnomAD4 genome AF: 0.0000133 AC: 1 AN: 74964 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 34338

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000420

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;