19-55455024-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136201.2(ISOC2):​c.502C>G​(p.Leu168Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,302 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ISOC2
NM_001136201.2 missense

Scores

2
12
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.45
Variant links:
Genes affected
ISOC2 (HGNC:26278): (isochorismatase domain containing 2) Involved in protein destabilization. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ISOC2NM_001136201.2 linkc.502C>G p.Leu168Val missense_variant Exon 5 of 6 ENST00000425675.7 NP_001129673.1 Q96AB3-1
ISOC2NM_024710.3 linkc.550C>G p.Leu184Val missense_variant Exon 5 of 6 NP_078986.1 Q96AB3-2
ISOC2NM_001136202.2 linkc.292C>G p.Leu98Val missense_variant Exon 4 of 5 NP_001129674.1 Q96AB3-3
ISOC2XM_047439445.1 linkc.340C>G p.Leu114Val missense_variant Exon 4 of 5 XP_047295401.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ISOC2ENST00000425675.7 linkc.502C>G p.Leu168Val missense_variant Exon 5 of 6 1 NM_001136201.2 ENSP00000401726.1 Q96AB3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461302
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
726956
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
.;T;.;T;T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.88
D;D;D;D;D
M_CAP
Benign
0.077
D
MetaRNN
Uncertain
0.65
D;D;D;D;D
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Pathogenic
3.4
.;M;.;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-2.6
D;D;D;.;.
REVEL
Benign
0.26
Sift
Uncertain
0.0020
D;D;D;.;.
Sift4G
Uncertain
0.0080
D;D;D;.;.
Polyphen
0.99
D;D;D;.;.
Vest4
0.68
MutPred
0.64
.;Loss of catalytic residue at L168 (P = 0.3551);.;Loss of catalytic residue at L168 (P = 0.3551);Loss of catalytic residue at L168 (P = 0.3551);
MVP
0.40
MPC
0.42
ClinPred
0.98
D
GERP RS
4.0
Varity_R
0.43
gMVP
0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55966391; API