chr2-8682409-C-G

Variant names:

• chr2-8682409-C-G
• rs763639723
• NM_002166.5:c.244C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002166.5(ID2):​c.244C>G​(p.His82Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H82N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ID2 NM_002166.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.79
• Publications: 0 publications found

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]

ID2 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3858731).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002166.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ID2	NM_002166.5	MANE Select	c.244C>G	p.His82Asp	missense	Exon 1 of 3	NP_002157.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ID2	ENST00000396290.2	TSL:1 MANE Select	c.244C>G	p.His82Asp	missense	Exon 1 of 3	ENSP00000379585.1	Q02363
	ID2	ENST00000234091.8	TSL:1	c.244C>G	p.His82Asp	missense	Exon 3 of 5	ENSP00000234091.4	Q02363
	ID2	ENST00000331129.3	TSL:1	c.244C>G	p.His82Asp	missense	Exon 1 of 2	ENSP00000385465.2	Q02363

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461556 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727086

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.80	D
Eigen	Benign	-0.030
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.77	D
MutationAssessor	Benign	1.9	L
PhyloP100		3.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.46
Sift	Benign	0.12	T
Sift4G	Benign	0.16	T
Polyphen		0.049	B
Vest4		0.54
MutPred		0.32		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.72
MPC		0.62
ClinPred		0.79	D
GERP RS		5.6
PromoterAI		0.098	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.62
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs763639723; hg19: chr2-8822539;