Variant chr2-118107180-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016133.4(INSIG2):c.627A>G(p.Gln209Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,608,662 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 90 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 62 hom. )

Consequence

INSIG2
NM_016133.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.225

Variant links:

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 links:

INSIG2 (HGNC:):

INSIG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 2-118107180-A-G is Benign according to our data. Variant chr2-118107180-A-G is described in ClinVar as [Benign]. Clinvar id is 780834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.225 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSIG2	NM_016133.4 linkuse as main transcript	c.627A>G	p.Gln209Gln	synonymous_variant	5/6	ENST00000245787.9	NP_057217.2	Q9Y5U4A0A024RAI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9 linkuse as main transcript	c.627A>G	p.Gln209Gln	synonymous_variant	5/6	1	NM_016133.4	ENSP00000245787.4		Q9Y5U4

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2911

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00545

AC:

1367

AN:

250714

Hom.:

AF XY:

0.00430

AC XY:

583

AN XY:

135450

show subpopulations

Gnomad AFR exome

AF:

0.0640

Gnomad AMR exome

AF:

0.00668

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000987

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000547

Gnomad OTH exome

AF:

0.00360

GnomAD4 exome

AF:

0.00226

AC:

3291

AN:

1456308

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1486

AN XY:

724832

show subpopulations

Gnomad4 AFR exome

AF:

0.0588

Gnomad4 AMR exome

AF:

0.00677

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.000782

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000552

Gnomad4 OTH exome

AF:

0.00533

GnomAD4 genome

AF:

0.0192

AC:

2924

AN:

152354

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1413

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0625

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00523

Hom.:

Bravo

AF:

0.0205

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000874

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.1

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over