11-64727506-ATTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTT

Variant names:

• chr11-64727506-A-ATT
• rs34854951
• NM_001098671.2:c.1772-148_1772-147dupAA

Variant summary

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

The NM_001098671.2(RASGRP2):​c.1772-148_1772-147dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000532 in 323,426 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 0.00044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00056 (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 = 0.00044 (33/74972) while in subpopulation AFR AF= 0.00141 (31/22050). AF 95% confidence interval is 0.00102. There are 0 homozygotes in gnomad4. There are 19 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.1772-148_1772-147dupAA		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_1772-146insAA		intron_variant	Intron 15 of 16	1	NM_001098671.2	ENSP00000377953.3

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 33 AN: 74958 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00141

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: 0.000559 AC: 139 AN: 248454 Hom.: 0 AF XY: 0.000496 AC XY: 67 AN XY: 135096

Gnomad4 AFR exome AF: 0.00432

Gnomad4 AMR exome AF: 0.000860

Gnomad4 ASJ exome AF: 0.000457

Gnomad4 EAS exome AF: 0.000657

Gnomad4 SAS exome AF: 0.000295

Gnomad4 FIN exome AF: 0.000264

Gnomad4 NFE exome AF: 0.000457

Gnomad4 OTH exome AF: 0.000628

GnomAD4 genome AF: 0.000440 AC: 33 AN: 74972 Hom.: 0 Cov.: 0 AF XY: 0.000553 AC XY: 19 AN XY: 34368

Gnomad4 AFR AF: 0.00141

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;