2-65313726-C-T
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_181784.3(SPRED2):c.1032G>A(p.Trp344*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SPRED2
NM_181784.3 stop_gained
NM_181784.3 stop_gained
Scores
4
2
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.17
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]
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ACMG classification
Classification made for transcript
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 0.179 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPRED2 | ENST00000356388.9 | c.1032G>A | p.Trp344* | stop_gained | Exon 6 of 6 | 1 | NM_181784.3 | ENSP00000348753.4 | ||
SPRED2 | ENST00000452315.5 | c.1077G>A | p.Trp359* | stop_gained | Exon 6 of 6 | 1 | ENSP00000390595.1 | |||
SPRED2 | ENST00000443619.6 | c.1023G>A | p.Trp341* | stop_gained | Exon 6 of 6 | 2 | ENSP00000393697.2 | |||
SPRED2 | ENST00000421087.5 | c.678G>A | p.Trp226* | stop_gained | Exon 3 of 3 | 3 | ENSP00000407627.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461856Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727230
GnomAD4 exome
AF:
AC:
2
AN:
1461856
Hom.:
Cov.:
34
AF XY:
AC XY:
2
AN XY:
727230
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at