2-8682859-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002166.5(ID2):​c.365C>T​(p.Ser122Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ID2
NM_002166.5 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.33
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ID2NM_002166.5 linkc.365C>T p.Ser122Phe missense_variant Exon 2 of 3 ENST00000396290.2 NP_002157.2 Q02363Q53T66

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ID2ENST00000396290.2 linkc.365C>T p.Ser122Phe missense_variant Exon 2 of 3 1 NM_002166.5 ENSP00000379585.1 Q02363
ID2ENST00000234091.8 linkc.365C>T p.Ser122Phe missense_variant Exon 4 of 5 1 ENSP00000234091.4 Q02363
ID2ENST00000331129.3 linkc.365C>T p.Ser122Phe missense_variant Exon 2 of 2 1 ENSP00000385465.2 Q02363
ID2ENST00000472142.1 linkn.80C>T non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461046
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726860
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 27, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.365C>T (p.S122F) alteration is located in exon 2 (coding exon 2) of the ID2 gene. This alteration results from a C to T substitution at nucleotide position 365, causing the serine (S) at amino acid position 122 to be replaced by a phenylalanine (F). 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
0.34
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.76
D;D;D
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.86
.;D;.
M_CAP
Benign
0.0086
T
MetaRNN
Uncertain
0.61
D;D;D
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
1.9
L;L;L
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-2.8
D;D;D
REVEL
Benign
0.22
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.011
D;D;D
Polyphen
0.74
P;P;P
Vest4
0.71
MutPred
0.30
Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);
MVP
0.29
MPC
0.75
ClinPred
0.98
D
GERP RS
5.6
Varity_R
0.28
gMVP
0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-8822989; API