rs764072860
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018993.4(RIN2):c.2336G>A(p.Arg779Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,603,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
RIN2
NM_018993.4 missense
NM_018993.4 missense
Scores
5
1
9
Clinical Significance
Conservation
PhyloP100: 6.94
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.23595819).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIN2 | NM_018993.4 | c.2336G>A | p.Arg779Gln | missense_variant | 12/13 | ENST00000255006.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIN2 | ENST00000255006.12 | c.2336G>A | p.Arg779Gln | missense_variant | 12/13 | 2 | NM_018993.4 | P1 | |
RIN2 | ENST00000440354.2 | c.1037G>A | p.Arg346Gln | missense_variant | 7/8 | 1 | |||
RIN2 | ENST00000484638.1 | n.2180G>A | non_coding_transcript_exon_variant | 8/9 | 1 | ||||
RIN2 | ENST00000648440.1 | c.2336G>A | p.Arg779Gln | missense_variant | 11/12 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152092Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000218 AC: 5AN: 229668Hom.: 0 AF XY: 0.0000161 AC XY: 2AN XY: 124070
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GnomAD4 exome AF: 0.0000138 AC: 20AN: 1451428Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 10AN XY: 720882
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74284
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 27, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 21, 2022 | The c.2336G>A (p.R779Q) alteration is located in exon 10 (coding exon 10) of the RIN2 gene. This alteration results from a G to A substitution at nucleotide position 2336, causing the arginine (R) at amino acid position 779 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
D;.;D
Vest4
0.73, 0.66
MVP
0.52
MPC
0.79
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