NM_001136201.2:c.293G>C

Variant names:

• chr19-55455691-C-G
• rs538150462
• NM_001136201.2:c.293G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136201.2(ISOC2):​c.293G>C​(p.Arg98Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,460 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R98Q) has been classified as Uncertain significance.

• 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: 0.425
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23964357).

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.293G>C	p.Arg98Pro	missense	Exon 3 of 6	NP_001129673.1	Q96AB3-1
	ISOC2	NM_024710.3		c.293G>C	p.Arg98Pro	missense	Exon 3 of 6	NP_078986.1	Q96AB3-2
	ISOC2	NM_001136202.2		c.139-361G>C		intron	N/A	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.293G>C	p.Arg98Pro	missense	Exon 3 of 6	ENSP00000401726.1	Q96AB3-1
	ISOC2	ENST00000085068.7	TSL:2	c.293G>C	p.Arg98Pro	missense	Exon 3 of 6	ENSP00000085068.2	Q96AB3-2
	ISOC2	ENST00000910877.1		c.293G>C	p.Arg98Pro	missense	Exon 4 of 7	ENSP00000580936.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458460 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 725038

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 85778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110554

Other (OTH) AF: 0.00 AC: 0 AN: 60170

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.075
Eigen_PC	Benign	-0.093
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.42
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.10
Sift	Benign	0.27	T
Sift4G	Benign	0.29	T
Polyphen		0.98	D
Vest4		0.30
MutPred		0.49		Gain of glycosylation at R98 (P = 0.0347)
MVP		0.52
MPC		0.35
ClinPred		0.51	D
GERP RS		3.3
Varity_R		0.24
gMVP		0.85
Mutation Taster		=66/34	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: rs538150462; hg19: chr19-55967058;