chr11-64727506-ATTTTTTTTTTTTTT-A

Variant names:

• chr11-64727506-ATTTTTTTTTTTTTT-A
• rs34854951
• NM_001098671.2:c.1772-160_1772-147delAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001098671.2(RASGRP2):​c.1772-160_1772-147delAAAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000402 in 248,852 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: RASGRP2 NM_001098671.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 0 publications found

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]

RASGRP2 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 18

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• osteopetrosis

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098671.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRP2	NM_001098671.2	MANE Select	c.1772-160_1772-147delAAAAAAAAAAAAAA		intron	N/A	NP_001092141.1	Q7LDG7-1
	RASGRP2	NM_001440703.1		c.1859-157_1859-144delAAAAAAAAAAAAAA		intron	N/A	NP_001427632.1
	RASGRP2	NM_001440704.1		c.1859-160_1859-147delAAAAAAAAAAAAAA		intron	N/A	NP_001427633.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRP2	ENST00000394432.8	TSL:1 MANE Select	c.1772-160_1772-147delAAAAAAAAAAAAAA		intron	N/A	ENSP00000377953.3	Q7LDG7-1
	RASGRP2	ENST00000354024.7	TSL:1	c.1772-160_1772-147delAAAAAAAAAAAAAA		intron	N/A	ENSP00000338864.3	Q7LDG7-1
	RASGRP2	ENST00000377497.7	TSL:1	c.1772-160_1772-147delAAAAAAAAAAAAAA		intron	N/A	ENSP00000366717.3	Q7LDG7-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000402 AC: 1 AN: 248852 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135316

African (AFR) AF: 0.00 AC: 0 AN: 6042

American (AMR) AF: 0.00 AC: 0 AN: 11646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6584

East Asian (EAS) AF: 0.00 AC: 0 AN: 13724

South Asian (SAS) AF: 0.00 AC: 0 AN: 37296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 992

European-Non Finnish (NFE) AF: 0.00000691 AC: 1 AN: 144656

Other (OTH) AF: 0.00 AC: 0 AN: 12764

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34854951; hg19: chr11-64494978;