NM_001098671.2:c.1772-149_1772-147dupAAA

Variant names:

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

Variant summary

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

The NM_001098671.2(RASGRP2):​c.1772-149_1772-147dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000988 in 323,758 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 0.000093 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (0 hom.)
• 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: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000934 (7/74978) while in subpopulation AFR AF= 0.000227 (5/22054). AF 95% confidence interval is 0.000089. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRP2	NM_001098671.2	c.1772-149_1772-147dupAAA		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_1772-146insAAA		intron_variant	Intron 15 of 16	1	NM_001098671.2	ENSP00000377953.3

Frequencies

GnomAD3 genomes AF: 0.0000934 AC: 7 AN: 74964 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000276

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000100 AC: 25 AN: 248780 Hom.: 0 AF XY: 0.000118 AC XY: 16 AN XY: 135278

Gnomad4 AFR exome AF: 0.000497

Gnomad4 AMR exome AF: 0.0000860

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000729

Gnomad4 SAS exome AF: 0.0000536

Gnomad4 FIN exome AF: 0.0000660

Gnomad4 NFE exome AF: 0.0000968

Gnomad4 OTH exome AF: 0.000157

GnomAD4 genome AF: 0.0000934 AC: 7 AN: 74978 Hom.: 0 Cov.: 0 AF XY: 0.000145 AC XY: 5 AN XY: 34370

Gnomad4 AFR AF: 0.000227

Gnomad4 AMR AF: 0.000157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000276

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;