chr15-38253190-GCGAGGAGACGGCGA-G

Position:

• chr15-38253190-GCGAGGAGACGGCGA-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_152594.3(SPRED1):​c.7_20del​(p.Glu3PhefsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPRED1 NM_152594.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.92

Genes affected

SPRED1 (HGNC:20249): (sprouty related EVH1 domain containing 1) The protein encoded by this gene is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth factors. The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade. Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 107 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-38253190-GCGAGGAGACGGCGA-G is Pathogenic according to our data. Variant chr15-38253190-GCGAGGAGACGGCGA-G is described in ClinVar as [Pathogenic]. Clinvar id is 547789.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-38253190-GCGAGGAGACGGCGA-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPRED1	NM_152594.3	c.7_20del	p.Glu3PhefsTer2	frameshift_variant	1/7	ENST00000299084.9
SPRED1	XM_005254202.4	c.7_20del	p.Glu3PhefsTer2	frameshift_variant	1/8
SPRED1	XM_047432199.1	c.-157_-144del		5_prime_UTR_variant	1/9
SPRED1	XM_047432200.1	c.-121_-108del		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRED1	ENST00000299084.9	c.7_20del	p.Glu3PhefsTer2	frameshift_variant	1/7	1	NM_152594.3	P1
SPRED1	ENST00000561317.1	c.-121_-108del		5_prime_UTR_variant	1/6	4
SPRED1	ENST00000561205.1	n.345_358del		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Legius syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Nov 01, 2016

- -

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: rs1555386651; hg19: chr15-38545391;