2-118097348-G-A

Variant names:

• chr2-118097348-G-A
• rs2042492
• NM_016133.4:c.244+548G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016133.4(INSIG2):​c.244+548G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,192 control chromosomes in the GnomAD database, including 4,757 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (4757 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 6 publications found

Genes affected

INSIG2 (HGNC:20452): (insulin induced gene 2) The protein encoded by this gene is highly similar to the protein product encoded by gene INSIG1. Both INSIG1 protein and this protein are endoplasmic reticulum proteins that block the processing of sterol regulatory element binding proteins (SREBPs) by binding to SREBP cleavage-activating protein (SCAP), and thus prevent SCAP from escorting SREBPs to the Golgi. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.244+548G>A		intron_variant	Intron 2 of 5	ENST00000245787.9	NP_057217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9	c.244+548G>A		intron_variant	Intron 2 of 5	1	NM_016133.4	ENSP00000245787.4

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37427 AN: 152074 Hom.: 4753 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.246 AC: 37453 AN: 152192 Hom.: 4757 Cov.: 32 AF XY: 0.244 AC XY: 18180 AN XY: 74424

African (AFR) AF: 0.276 AC: 11464 AN: 41506

American (AMR) AF: 0.189 AC: 2897 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3472

East Asian (EAS) AF: 0.114 AC: 590 AN: 5186

South Asian (SAS) AF: 0.254 AC: 1228 AN: 4828

European-Finnish (FIN) AF: 0.185 AC: 1960 AN: 10590

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17642 AN: 68002

Other (OTH) AF: 0.234 AC: 493 AN: 2110

Alfa AF: 0.260 Hom.: 874

Bravo AF: 0.243

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.029
DANN	Benign	0.34
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs2042492; hg19: chr2-118854924;