rs776334940

Variant names:

• chr19-55455773-C-G
• NM_001136201.2:c.211G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-55455773-C-G
• chr19-55455773-C-T

Variant summary

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

The NM_001136201.2(ISOC2):​c.211G>C​(p.Glu71Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,425,410 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: 0.0000021 (0 hom.)
• Consequence: ISOC2 NM_001136201.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43

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.211G>C	p.Glu71Gln	missense_variant	Exon 3 of 6	ENST00000425675.7	NP_001129673.1
ISOC2	NM_024710.3	c.211G>C	p.Glu71Gln	missense_variant	Exon 3 of 6		NP_078986.1
ISOC2	NM_001136202.2	c.139-443G>C		intron_variant	Intron 2 of 4		NP_001129674.1
ISOC2	XM_047439445.1	c.139-395G>C		intron_variant	Intron 2 of 4		XP_047295401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISOC2	ENST00000425675.7	c.211G>C	p.Glu71Gln	missense_variant	Exon 3 of 6	1	NM_001136201.2	ENSP00000401726.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1425410 Hom.: 0 Cov.: 33 AF XY: 0.00000142 AC XY: 1 AN XY: 705732

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: 0.00000274

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	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.6	M;M;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.7	D;D;.;.
REVEL	Benign	0.24
Sift	Benign	0.047	D;T;.;.
Sift4G	Uncertain	0.0090	D;D;.;.
Polyphen		0.99	D;D;.;.
Vest4		0.29
MutPred		0.44		Gain of glycosylation at T68 (P = 0.1411);Gain of glycosylation at T68 (P = 0.1411);Gain of glycosylation at T68 (P = 0.1411);Gain of glycosylation at T68 (P = 0.1411);
MVP		0.69
MPC		0.44
ClinPred		0.93	D
GERP RS		4.4
Varity_R		0.37
gMVP		0.77

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: chr19-55967140;