rs779830218

Variant names:

• chr19-55455296-T-G
• rs779830218
• NM_001136201.2:c.383A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-55455296-T-G
• chr19-55455296-T-A
• chr19-55455296-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001136201.2(ISOC2):​c.383A>C​(p.Gln128Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ISOC2 NM_001136201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISOC2	NM_001136201.2	MANE Select	c.383A>C	p.Gln128Pro	missense	Exon 4 of 6	NP_001129673.1	Q96AB3-1
	ISOC2	NM_024710.3		c.431A>C	p.Gln144Pro	missense	Exon 4 of 6	NP_078986.1	Q96AB3-2
	ISOC2	NM_001136202.2		c.173A>C	p.Gln58Pro	missense	Exon 3 of 5	NP_001129674.1	Q96AB3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISOC2	ENST00000425675.7	TSL:1 MANE Select	c.383A>C	p.Gln128Pro	missense	Exon 4 of 6	ENSP00000401726.1	Q96AB3-1
	ISOC2	ENST00000085068.7	TSL:2	c.431A>C	p.Gln144Pro	missense	Exon 4 of 6	ENSP00000085068.2	Q96AB3-2
	ISOC2	ENST00000910877.1		c.431A>C	p.Gln144Pro	missense	Exon 5 of 7	ENSP00000580936.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.3
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.19
Sift	Benign	0.039	D
Sift4G	Benign	0.091	T
Polyphen		0.98	D
Vest4		0.52
MutPred		0.52		Gain of catalytic residue at L127 (P = 0.1611)
MVP		0.45
MPC		0.096
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.42
gMVP		0.81
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs779830218; hg19: chr19-55966663;