rs368903840

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-55455024-G-A
• chr19-55455024-G-C
• chr19-55455024-G-T

Variant summary

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

The NM_001136201.2(ISOC2):​c.502C>T​(p.Leu168Phe) 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>T	p.Leu168Phe	missense_variant	Exon 5 of 6	ENST00000425675.7	NP_001129673.1
ISOC2	NM_024710.3	c.550C>T	p.Leu184Phe	missense_variant	Exon 5 of 6		NP_078986.1
ISOC2	NM_001136202.2	c.292C>T	p.Leu98Phe	missense_variant	Exon 4 of 5		NP_001129674.1
ISOC2	XM_047439445.1	c.340C>T	p.Leu114Phe	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>T	p.Leu168Phe	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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;.;T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.73	D;D;D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.8	.;M;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.7	D;D;D;.;.
REVEL	Pathogenic	0.66
Sift	Uncertain	0.018	D;D;D;.;.
Sift4G	Benign	0.086	T;T;T;.;.
Polyphen		0.98	D;D;P;.;.
Vest4		0.72
MutPred		0.58		.;Gain of catalytic residue at L168 (P = 0.3031);.;Gain of catalytic residue at L168 (P = 0.3031);Gain of catalytic residue at L168 (P = 0.3031);
MVP		0.43
MPC		0.46
ClinPred		0.99	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.31
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55966391;