chr2-65313614-TAA-T

Position:

• chr2-65313614-TAA-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_181784.3(SPRED2):​c.1142_1143del​(p.Leu381HisfsTer95) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPRED2 NM_181784.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 9.32

Genes affected

SPRED2 (HGNC:17722): (sprouty related EVH1 domain containing 2) SPRED2 is a member of the Sprouty (see SPRY1; MIM 602465)/SPRED family of proteins that regulate growth factor-induced activation of the MAP kinase cascade (see MAPK1; MIM 176948) (Nonami et al., 2004 [PubMed 15465815]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0915 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-65313614-TAA-T is Pathogenic according to our data. Variant chr2-65313614-TAA-T is described in ClinVar as [Pathogenic]. Clinvar id is 1209657.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-65313614-TAA-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPRED2	NM_181784.3	c.1142_1143del	p.Leu381HisfsTer95	frameshift_variant	6/6	ENST00000356388.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRED2	ENST00000356388.9	c.1142_1143del	p.Leu381HisfsTer95	frameshift_variant	6/6	1	NM_181784.3	P4
SPRED2	ENST00000452315.5	c.1187_1188del	p.Leu396HisfsTer?	frameshift_variant	6/6	1
SPRED2	ENST00000443619.6	c.1133_1134del	p.Leu378HisfsTer95	frameshift_variant	6/6	2		A1

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

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Noonan syndrome 14 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 15, 2022

- -

Noonan syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Tartaglia Lab, Genetics and Rare Diseases Research Division, Bambino Gesu' Children's Hospital

Aug 01, 2021

- -

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-65540748;