Genetic Variant ISOC2:p.Gln128Arg (chr19-55455296-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001136201.2(ISOC2):c.383A>G(p.Gln128Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,484 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q128P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 1 hom. )

Consequence

ISOC2
NM_001136201.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.34

Publications

0 publications found

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]

ISOC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3206306).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136201.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ISOC2	NM_001136201.2	MANE Select	c.383A>G	p.Gln128Arg	missense	Exon 4 of 6	NP_001129673.1	Q96AB3-1
ISOC2	NM_024710.3		c.431A>G	p.Gln144Arg	missense	Exon 4 of 6	NP_078986.1	Q96AB3-2
ISOC2	NM_001136202.2		c.173A>G	p.Gln58Arg	missense	Exon 3 of 5	NP_001129674.1	Q96AB3-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ISOC2	ENST00000425675.7	TSL:1 MANE Select	c.383A>G	p.Gln128Arg	missense	Exon 4 of 6	ENSP00000401726.1	Q96AB3-1
ISOC2	ENST00000085068.7	TSL:2	c.431A>G	p.Gln144Arg	missense	Exon 4 of 6	ENSP00000085068.2	Q96AB3-2
ISOC2	ENST00000910877.1		c.431A>G	p.Gln144Arg	missense	Exon 5 of 7	ENSP00000580936.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

249114

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461484

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000116

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111816

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

0.054

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.015

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

2.3

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.0

REVEL

Benign

0.074

Sift

Benign

0.069

Sift4G

Benign

0.38

Polyphen

0.76

Vest4

0.40

MutPred

0.44

Gain of catalytic residue at Q128 (P = 0.2185)

MVP

0.40

MPC

0.12

ClinPred

0.29

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.51

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over