2-118089309-T-C

Position:

• chr2-118089309-T-C

Variant summary

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

The NM_016133.4(INSIG2):​c.-139+768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,044 control chromosomes in the GnomAD database, including 20,718 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 0.52 (20718 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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]

INSIG2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.-139+768T>C		intron_variant		ENST00000245787.9	NP_057217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9	c.-139+768T>C		intron_variant		1	NM_016133.4	ENSP00000245787.4

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78527 AN: 151928 Hom.: 20716 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.517 AC: 78570 AN: 152044 Hom.: 20718 Cov.: 32 AF XY: 0.515 AC XY: 38256 AN XY: 74332

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.556

Alfa AF: 0.547 Hom.: 4641

Bravo AF: 0.510

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.64

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: rs13428113; hg19: chr2-118846885; COSMIC: COSV55522779;