4-183510641-C-A

Position:

• chr4-183510641-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001564.4(ING2):​c.532C>A​(p.Pro178Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ING2 NM_001564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73

Genes affected

ING2 (HGNC:6063): (inhibitor of growth family member 2) This gene is a member of the inhibitor of growth (ING) family. Members of the ING family associate with and modulate the activity of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes and function in DNA repair and apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

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/exons	MANE	UniProt
ING2	NM_001564.4	c.532C>A	p.Pro178Thr	missense_variant	2/2	ENST00000302327.4
ING2	NM_001291959.2	c.412C>A	p.Pro138Thr	missense_variant	2/2
ING2	XM_011531927.3	c.367C>A	p.Pro123Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ING2	ENST00000302327.4	c.532C>A	p.Pro178Thr	missense_variant	2/2	1	NM_001564.4	P1
ING2	ENST00000412117.1	c.412C>A	p.Pro138Thr	missense_variant	2/2	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.532C>A (p.P178T) alteration is located in exon 2 (coding exon 2) of the ING2 gene. This alteration results from a C to A substitution at nucleotide position 532, causing the proline (P) at amino acid position 178 to be replaced by a threonine (T). 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	0.099
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.46	T;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.4	D;N
REVEL	Uncertain	0.38
Sift	Benign	0.076	T;D
Sift4G	Benign	0.11	T;D
Polyphen		0.58	P;.
Vest4		0.38
MutPred		0.27		Gain of glycosylation at S183 (P = 0.0035);.;
MVP		1.0
MPC		0.92
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.24
gMVP		0.26

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: chr4-184431794;