rs727502782

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The ENST00000264896.8(SCARB2):​c.1258del​(p.Glu420ArgfsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

SCARB2
ENST00000264896.8 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 3.59
Variant links:
Genes affected
SCARB2 (HGNC:1665): (scavenger receptor class B member 2) The protein encoded by this gene is a type III glycoprotein that is located primarily in limiting membranes of lysosomes and endosomes. Earlier studies in mice and rat suggested that this protein may participate in membrane transportation and the reorganization of endosomal/lysosomal compartment. The protein deficiency in mice was reported to impair cell membrane transport processes and cause pelvic junction obstruction, deafness, and peripheral neuropathy. Further studies in human showed that this protein is a ubiquitously expressed protein and that it is involved in the pathogenesis of HFMD (hand, foot, and mouth disease) caused by enterovirus-71 and possibly by coxsackievirus A16. Mutations in this gene caused an autosomal recessive progressive myoclonic epilepsy-4 (EPM4), also known as action myoclonus-renal failure syndrome (AMRF). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 4-76163364-TC-T is Pathogenic according to our data. Variant chr4-76163364-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 30258.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SCARB2NM_005506.4 linkuse as main transcriptc.1258del p.Glu420ArgfsTer6 frameshift_variant 11/12 ENST00000264896.8 NP_005497.1
SCARB2NM_001204255.2 linkuse as main transcriptc.829del p.Glu277ArgfsTer6 frameshift_variant 8/9 NP_001191184.1
SCARB2XM_047416429.1 linkuse as main transcriptc.784del p.Glu262ArgfsTer6 frameshift_variant 11/12 XP_047272385.1
SCARB2XM_047416430.1 linkuse as main transcriptc.784del p.Glu262ArgfsTer6 frameshift_variant 11/12 XP_047272386.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SCARB2ENST00000264896.8 linkuse as main transcriptc.1258del p.Glu420ArgfsTer6 frameshift_variant 11/121 NM_005506.4 ENSP00000264896 P4Q14108-1
ENST00000651366.1 linkuse as main transcriptn.102+14099del intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

Action myoclonus-renal failure syndrome Pathogenic:1Other:1
not provided, no classification providedliterature onlyGeneReviews-- -
Pathogenic, no assertion criteria providedliterature onlyOMIMOct 01, 2009- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs727502782; hg19: chr4-77084517; API