2-8682442-C-T

Variant names:

• chr2-8682442-C-T
• NM_002166.5:c.277C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002166.5(ID2):​c.277C>T​(p.Pro93Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,434 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: 6.8e-7 (0 hom.)
• Consequence: ID2 NM_002166.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.34

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2894047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID2	NM_002166.5	c.277C>T	p.Pro93Ser	missense_variant	Exon 1 of 3	ENST00000396290.2	NP_002157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ID2	ENST00000396290.2	c.277C>T	p.Pro93Ser	missense_variant	Exon 1 of 3	1	NM_002166.5	ENSP00000379585.1
ID2	ENST00000234091.8	c.277C>T	p.Pro93Ser	missense_variant	Exon 3 of 5	1		ENSP00000234091.4
ID2	ENST00000331129.3	c.277C>T	p.Pro93Ser	missense_variant	Exon 1 of 2	1		ENSP00000385465.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461434 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727024

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.277C>T (p.P93S) alteration is located in exon 1 (coding exon 1) of the ID2 gene. This alteration results from a C to T substitution at nucleotide position 277, causing the proline (P) at amino acid position 93 to be replaced by a serine (S). 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	0.084
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;D;D
Eigen	Benign	-0.049
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	.;D;.
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.57
Sift	Benign	0.052	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.099	B;B;B
Vest4		0.31
MutPred		0.090		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.79
MPC		0.46
ClinPred		0.83	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.47

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: chr2-8822572;