chr2-118111006-G-C

Position:

• chr2-118111006-G-C

Variant summary

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

The variant allele was found at a frequency of 0.23 in 152,126 control chromosomes in the GnomAD database, including 4,936 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 0.23 (4936 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897

Genes affected

(HGNC:):

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.*2684G>C		downstream_gene_variant		ENST00000245787.9	NP_057217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9	c.*2684G>C		downstream_gene_variant		1	NM_016133.4	ENSP00000245787.4
INSIG2	ENST00000485520.5	n.*9G>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34893 AN: 152008 Hom.: 4927 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.221

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.230 AC: 34948 AN: 152126 Hom.: 4936 Cov.: 33 AF XY: 0.228 AC XY: 16955 AN XY: 74358

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.224

Alfa AF: 0.213 Hom.: 491

Bravo AF: 0.240

Asia WGS AF: 0.112 AC: 392 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17047764; hg19: chr2-118868582;