19-55455024-G-C

Variant names:

• chr19-55455024-G-C
• NM_001136201.2:c.502C>G

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 𝑓: 6.8e-7 (0 hom.)
• Consequence: ISOC2 NM_001136201.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.45

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]

ACMG classification

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
ISOC2	NM_001136201.2	c.502C>G	p.Leu168Val	missense_variant	Exon 5 of 6	ENST00000425675.7	NP_001129673.1
ISOC2	NM_024710.3	c.550C>G	p.Leu184Val	missense_variant	Exon 5 of 6		NP_078986.1
ISOC2	NM_001136202.2	c.292C>G	p.Leu98Val	missense_variant	Exon 4 of 5		NP_001129674.1
ISOC2	XM_047439445.1	c.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
ISOC2	ENST00000425675.7	c.502C>G	p.Leu168Val	missense_variant	Exon 5 of 6	1	NM_001136201.2	ENSP00000401726.1

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

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;