chr2-8682427-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002166.5(ID2):​c.262C>G​(p.Leu88Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ID2
NM_002166.5 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22554582).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ID2NM_002166.5 linkc.262C>G p.Leu88Val missense_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.262C>G p.Leu88Val missense_variant Exon 1 of 3 1 NM_002166.5 ENSP00000379585.1 Q02363
ID2ENST00000234091.8 linkc.262C>G p.Leu88Val missense_variant Exon 3 of 5 1 ENSP00000234091.4 Q02363
ID2ENST00000331129.3 linkc.262C>G p.Leu88Val missense_variant Exon 1 of 2 1 ENSP00000385465.2 Q02363

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461508
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727058
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.262C>G (p.L88V) alteration is located in exon 1 (coding exon 1) of the ID2 gene. This alteration results from a C to G substitution at nucleotide position 262, causing the leucine (L) at amino acid position 88 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.37
T;T;T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.049
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.74
.;T;.
M_CAP
Uncertain
0.19
D
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Uncertain
0.71
D
MutationAssessor
Benign
2.0
M;M;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.58
N;N;N
REVEL
Uncertain
0.47
Sift
Benign
0.37
T;T;T
Sift4G
Benign
0.45
T;T;T
Polyphen
0.085
B;B;B
Vest4
0.42
MutPred
0.19
Loss of catalytic residue at L88 (P = 0.1358);Loss of catalytic residue at L88 (P = 0.1358);Loss of catalytic residue at L88 (P = 0.1358);
MVP
0.70
MPC
0.44
ClinPred
0.59
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.32
gMVP
0.39

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: rs765612480; hg19: chr2-8822557; API