rs137852213

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001272071.2(AP1S2):​c.226G>T​(p.Glu76Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 23)

Consequence

AP1S2
NM_001272071.2 stop_gained

Scores

3
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
AP1S2 (HGNC:560): (adaptor related protein complex 1 subunit sigma 2) Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large, one medium, and one small adaptin subunit. The protein encoded by this gene serves as the small subunit of this complex and is a member of the adaptin protein family. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-15845965-C-A is Pathogenic according to our data. Variant chrX-15845965-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 10781.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-15845965-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AP1S2NM_001272071.2 linkuse as main transcriptc.226G>T p.Glu76Ter stop_gained 3/6 ENST00000672987.1 NP_001259000.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AP1S2ENST00000672987.1 linkuse as main transcriptc.226G>T p.Glu76Ter stop_gained 3/6 NM_001272071.2 ENSP00000500695 P3

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Pettigrew syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMNov 01, 2007- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.66
CADD
Pathogenic
37
DANN
Uncertain
1.0
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
A;A;A;A
Vest4
0.54
ClinPred
1.0
D
GERP RS
5.9

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs137852213; hg19: chrX-15864088; API