rs759390822
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_018993.4(RIN2):c.1731del(p.Ile578SerfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RIN2
NM_018993.4 frameshift
NM_018993.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0610
Genes affected
RIN2 (HGNC:18750): (Ras and Rab interactor 2) The RAB5 protein is a small GTPase involved in membrane trafficking in the early endocytic pathway. The protein encoded by this gene binds the GTP-bound form of the RAB5 protein preferentially over the GDP-bound form, and functions as a guanine nucleotide exchange factor for RAB5. The encoded protein is found primarily as a tetramer in the cytoplasm and does not bind other members of the RAB family. Mutations in this gene cause macrocephaly alopecia cutis laxa and scoliosis (MACS) syndrome, an elastic tissue disorder, as well as the related connective tissue disorder, RIN2 syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]
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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 20-19975749-AC-A is Pathogenic according to our data. Variant chr20-19975749-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 1296.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIN2 | NM_018993.4 | c.1731del | p.Ile578SerfsTer4 | frameshift_variant | 9/13 | ENST00000255006.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIN2 | ENST00000255006.12 | c.1731del | p.Ile578SerfsTer4 | frameshift_variant | 9/13 | 2 | NM_018993.4 | P1 | |
RIN2 | ENST00000440354.2 | c.464-14250del | intron_variant | 1 | |||||
RIN2 | ENST00000484638.1 | n.1575del | non_coding_transcript_exon_variant | 5/9 | 1 | ||||
RIN2 | ENST00000648440.1 | c.1731del | p.Ile578SerfsTer4 | frameshift_variant | 8/12 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460118Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 726274
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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1460118
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36
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0
AN XY:
726274
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
RIN2 syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2014 | - - |
Computational scores
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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