2-8682859-C-T

Variant names:

• chr2-8682859-C-T
• NM_002166.5:c.365C>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.33

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 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
ID2	NM_002166.5	c.365C>T	p.Ser122Phe	missense_variant	Exon 2 of 3	ENST00000396290.2	NP_002157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ID2	ENST00000396290.2	c.365C>T	p.Ser122Phe	missense_variant	Exon 2 of 3	1	NM_002166.5	ENSP00000379585.1
ID2	ENST00000234091.8	c.365C>T	p.Ser122Phe	missense_variant	Exon 4 of 5	1		ENSP00000234091.4
ID2	ENST00000331129.3	c.365C>T	p.Ser122Phe	missense_variant	Exon 2 of 2	1		ENSP00000385465.2
ID2	ENST00000472142.1	n.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

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

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;