chr19-6772948-TAAC-T

Position:

• chr19-6772948-TAAC-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The ENST00000602142.6(VAV1):​c.145_147delAAC​(p.Asn49del) variant causes a conservative inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VAV1 ENST00000602142.6 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.96

Genes affected

VAV1 (HGNC:12657): (vav guanine nucleotide exchange factor 1) This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. The encoded protein is important in hematopoiesis, playing a role in T-cell and B-cell development and activation. The encoded protein has been identified as the specific binding partner of Nef proteins from HIV-1. Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000602142.6. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV1	NM_005428.4	c.145_147delAAC	p.Asn49del	conservative_inframe_deletion	1/27	ENST00000602142.6	NP_005419.2
VAV1	NM_001258206.2	c.145_147delAAC	p.Asn49del	conservative_inframe_deletion	1/26		NP_001245135.1
VAV1	NM_001258207.2	c.145_147delAAC	p.Asn49del	conservative_inframe_deletion	1/26		NP_001245136.1
VAV1	XM_005259642.2	c.145_147delAAC	p.Asn49del	conservative_inframe_deletion	1/26		XP_005259699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV1	ENST00000602142.6	c.145_147delAAC	p.Asn49del	conservative_inframe_deletion	1/27	1	NM_005428.4	ENSP00000472929.1
VAV1	ENST00000304076.6	c.145_147delAAC	p.Asn49del	conservative_inframe_deletion	1/26	1		ENSP00000302269.2
VAV1	ENST00000596764.5	c.145_147delAAC	p.Asn49del	conservative_inframe_deletion	1/26	2		ENSP00000469450.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2020

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with VAV1-related conditions. This variant is not present in population databases (ExAC no frequency). This variant, c.145_147del, results in the deletion of 1 amino acid(s) of the VAV1 protein (p.Asn49del), but otherwise preserves the integrity of the reading frame. -

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: rs1310252736; hg19: chr19-6772959;