chr4-17515274-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001079827.2(CLRN2):c.8G>T(p.Gly3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,782 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 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
CLRN2
NM_001079827.2 missense
NM_001079827.2 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 3.17
Genes affected
CLRN2 (HGNC:33939): (clarin 2) This gene belongs to the clarin family of genes. The clarins appear to belong to a large superfamily of small integral membrane glycoproteins with four transmembrane domains. The exact function of this gene is unknown. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.30076253).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLRN2 | NM_001079827.2 | c.8G>T | p.Gly3Val | missense_variant | 1/3 | ENST00000511148.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLRN2 | ENST00000511148.2 | c.8G>T | p.Gly3Val | missense_variant | 1/3 | 1 | NM_001079827.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152216Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249060Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135116
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461448Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727000
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74488
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2023 | The c.8G>T (p.G3V) alteration is located in exon 1 (coding exon 1) of the CLRN2 gene. This alteration results from a G to T substitution at nucleotide position 8, causing the glycine (G) at amino acid position 3 to be replaced by a valine (V). 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
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
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