chr2-118098580-G-A

Position:

• chr2-118098580-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016133.4(INSIG2):​c.244+1780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 152,264 control chromosomes in the GnomAD database, including 373 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 0.054 (373 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.244+1780G>A		intron_variant		ENST00000245787.9	NP_057217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9	c.244+1780G>A		intron_variant		1	NM_016133.4	ENSP00000245787	P1

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8264 AN: 152146 Hom.: 372 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0422

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0439

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

GnomAD4 genome AF: 0.0543 AC: 8273 AN: 152264 Hom.: 373 Cov.: 32 AF XY: 0.0598 AC XY: 4452 AN XY: 74436

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0946

Gnomad4 ASJ AF: 0.0456

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.0594

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0569 Hom.: 138

Bravo AF: 0.0479

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs17528324; hg19: chr2-118856156; COSMIC: COSV55522193; COSMIC: COSV55522193;