chr2-8682268-C-T

Variant names:

• chr2-8682268-C-T
• rs114406044
• NM_002166.5:c.103C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_002166.5(ID2):​c.103C>T​(p.Leu35Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,138 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (43 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (40 hom.)
• Consequence: ID2 NM_002166.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.69
• Publications: 2 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 2-8682268-C-T is Benign according to our data. Variant chr2-8682268-C-T is described in ClinVar as Benign. ClinVar VariationId is 783971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.69 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0115 (1757/152328) while in subpopulation AFR AF = 0.0404 (1679/41568). AF 95% confidence interval is 0.0388. There are 43 homozygotes in GnomAd4. There are 865 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1757 AD gene.

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.103C>T	p.Leu35Leu	synonymous	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.103C>T	p.Leu35Leu	synonymous	Exon 1 of 3	ENSP00000379585.1	Q02363
	ID2	ENST00000234091.8	TSL:1	c.103C>T	p.Leu35Leu	synonymous	Exon 3 of 5	ENSP00000234091.4	Q02363
	ID2	ENST00000331129.3	TSL:1	c.103C>T	p.Leu35Leu	synonymous	Exon 1 of 2	ENSP00000385465.2	Q02363

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1755 AN: 152210 Hom.: 43 Cov.: 31

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

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: 0.000103

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00308 AC: 775 AN: 251306 AF XY: 0.00230

Gnomad AFR exome AF: 0.0428

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00121 AC: 1764 AN: 1461810 Hom.: 40 Cov.: 32 AF XY: 0.000965 AC XY: 702 AN XY: 727210

African (AFR) AF: 0.0423 AC: 1416 AN: 33480

American (AMR) AF: 0.00172 AC: 77 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: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0000845 AC: 94 AN: 1111998

Other (OTH) AF: 0.00262 AC: 158 AN: 60388

GnomAD4 genome AF: 0.0115 AC: 1757 AN: 152328 Hom.: 43 Cov.: 31 AF XY: 0.0116 AC XY: 865 AN XY: 74482

African (AFR) AF: 0.0404 AC: 1679 AN: 41568

American (AMR) AF: 0.00327 AC: 50 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68032

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00475 Hom.: 6

Bravo AF: 0.0132

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		2.7
PromoterAI		-0.022	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114406044; hg19: chr2-8822398;