chr17-46923194-T-G
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5
The NM_004287.5(GOSR2):c.2T>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000905 in 1,546,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000079 ( 0 hom. )
Consequence
GOSR2
NM_004287.5 start_lost
NM_004287.5 start_lost
Scores
4
6
1
Clinical Significance
Conservation
PhyloP100: 3.77
Genes affected
GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_004287.5 (GOSR2) was described as [Conflicting_classifications_of_pathogenicity] in ClinVar as 1061696
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-46923194-T-G is Pathogenic according to our data. Variant chr17-46923194-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1324496.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GOSR2 | NM_004287.5 | c.2T>G | p.Met1? | start_lost | 1/6 | ENST00000640051.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GOSR2 | ENST00000640051.2 | c.2T>G | p.Met1? | start_lost | 1/6 | 1 | NM_004287.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000194 AC: 3AN: 154276Hom.: 0 AF XY: 0.0000368 AC XY: 3AN XY: 81610
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GnomAD4 exome AF: 0.00000789 AC: 11AN: 1394036Hom.: 0 Cov.: 30 AF XY: 0.00000872 AC XY: 6AN XY: 687870
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Muscular dystrophy, congenital, with or without seizures Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 22, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D
Polyphen
0.99, 0.95
.;.;.;D;.;.;P;.;.;.;.;.;.;.
Vest4
0.80, 0.78, 0.77, 0.79
MVP
0.91
ClinPred
D
GERP RS
Varity_R
gMVP
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