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GeneBe

2-118103297-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_016133.4(INSIG2):c.345T>C(p.Phe115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,613,400 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0047 ( 30 hom. )

Consequence

INSIG2
NM_016133.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-118103297-T-C is Benign according to our data. Variant chr2-118103297-T-C is described in ClinVar as [Benign]. Clinvar id is 770694.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.28 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00469 (6848/1461094) while in subpopulation MID AF= 0.0368 (212/5764). AF 95% confidence interval is 0.0327. There are 30 homozygotes in gnomad4_exome. There are 3467 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
INSIG2NM_016133.4 linkuse as main transcriptc.345T>C p.Phe115= synonymous_variant 3/6 ENST00000245787.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
INSIG2ENST00000245787.9 linkuse as main transcriptc.345T>C p.Phe115= synonymous_variant 3/61 NM_016133.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00441
AC:
671
AN:
152188
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000965
Gnomad AMI
AF:
0.0285
Gnomad AMR
AF:
0.00837
Gnomad ASJ
AF:
0.0121
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.00207
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.00556
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.00475
AC:
1193
AN:
251130
Hom.:
6
AF XY:
0.00498
AC XY:
676
AN XY:
135722
show subpopulations
Gnomad AFR exome
AF:
0.000554
Gnomad AMR exome
AF:
0.00538
Gnomad ASJ exome
AF:
0.0128
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00386
Gnomad FIN exome
AF:
0.00166
Gnomad NFE exome
AF:
0.00586
Gnomad OTH exome
AF:
0.00817
GnomAD4 exome
AF:
0.00469
AC:
6848
AN:
1461094
Hom.:
30
Cov.:
31
AF XY:
0.00477
AC XY:
3467
AN XY:
726880
show subpopulations
Gnomad4 AFR exome
AF:
0.000956
Gnomad4 AMR exome
AF:
0.00512
Gnomad4 ASJ exome
AF:
0.0112
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00394
Gnomad4 FIN exome
AF:
0.00191
Gnomad4 NFE exome
AF:
0.00477
Gnomad4 OTH exome
AF:
0.00553
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00440
AC:
670
AN:
152306
Hom.:
4
Cov.:
32
AF XY:
0.00439
AC XY:
327
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000962
Gnomad4 AMR
AF:
0.00836
Gnomad4 ASJ
AF:
0.0121
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.00207
Gnomad4 NFE
AF:
0.00556
Gnomad4 OTH
AF:
0.00757
Alfa
AF:
0.00564
Hom.:
3
Bravo
AF:
0.00480
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
10
Dann
Benign
0.77
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.

Other links and lift over

dbSNP: rs35551800; hg19: chr2-118860873; COSMIC: COSV55523481; COSMIC: COSV55523481; API