2-8682427-C-G

Variant names:

• chr2-8682427-C-G
• rs765612480
• NM_002166.5:c.262C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

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 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
ID2	NM_002166.5	c.262C>G	p.Leu88Val	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.262C>G	p.Leu88Val	missense_variant	Exon 1 of 3	1	NM_002166.5	ENSP00000379585.1
ID2	ENST00000234091.8	c.262C>G	p.Leu88Val	missense_variant	Exon 3 of 5	1		ENSP00000234091.4
ID2	ENST00000331129.3	c.262C>G	p.Leu88Val	missense_variant	Exon 1 of 2	1		ENSP00000385465.2

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

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

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

Other links and lift over

dbSNP: rs765612480; hg19: chr2-8822557;