2-8682268-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_002166.5(ID2):​c.103C>T​(p.Leu35Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,138 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 43 hom., cov: 31)
Exomes 𝑓: 0.0012 ( 40 hom. )

Consequence

ID2
NM_002166.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 2.69
Variant links:
Genes affected
ID2 (HGNC:5361): (inhibitor of DNA binding 2) The protein encoded by this gene belongs to the inhibitor of DNA binding family, members of which are transcriptional regulators that contain a helix-loop-helix (HLH) domain but not a basic domain. Members of the inhibitor of DNA binding family inhibit the functions of basic helix-loop-helix transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains. This protein may play a role in negatively regulating cell differentiation. A pseudogene of this gene is located on chromosome 3. [provided by RefSeq, Aug 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
Variant 2-8682268-C-T is Benign according to our data. Variant chr2-8682268-C-T is described in ClinVar as [Benign]. Clinvar id is 783971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.69 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1757/152328) while in subpopulation AFR AF= 0.0404 (1679/41568). AF 95% confidence interval is 0.0388. There are 43 homozygotes in gnomad4. There are 865 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1757 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ID2NM_002166.5 linkc.103C>T p.Leu35Leu synonymous_variant Exon 1 of 3 ENST00000396290.2 NP_002157.2 Q02363Q53T66

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ID2ENST00000396290.2 linkc.103C>T p.Leu35Leu synonymous_variant Exon 1 of 3 1 NM_002166.5 ENSP00000379585.1 Q02363
ID2ENST00000234091.8 linkc.103C>T p.Leu35Leu synonymous_variant Exon 3 of 5 1 ENSP00000234091.4 Q02363
ID2ENST00000331129.3 linkc.103C>T p.Leu35Leu synonymous_variant Exon 1 of 2 1 ENSP00000385465.2 Q02363

Frequencies

GnomAD3 genomes
AF:
0.0115
AC:
1755
AN:
152210
Hom.:
43
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0405
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.00308
AC:
775
AN:
251306
Hom.:
16
AF XY:
0.00230
AC XY:
312
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.0428
Gnomad AMR exome
AF:
0.00139
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000158
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00121
AC:
1764
AN:
1461810
Hom.:
40
Cov.:
32
AF XY:
0.000965
AC XY:
702
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0423
Gnomad4 AMR exome
AF:
0.00172
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000845
Gnomad4 OTH exome
AF:
0.00262
GnomAD4 genome
AF:
0.0115
AC:
1757
AN:
152328
Hom.:
43
Cov.:
31
AF XY:
0.0116
AC XY:
865
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0404
Gnomad4 AMR
AF:
0.00327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00993
Alfa
AF:
0.00494
Hom.:
5
Bravo
AF:
0.0132
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Sep 14, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
CADD
Benign
13
DANN
Benign
0.92

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: rs114406044; hg19: chr2-8822398; API