2-241702073-C-G

Variant names:

• chr2-241702073-C-G
• rs946862250
• NM_032329.6:c.8C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032329.6(ING5):​c.8C>G​(p.Thr3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000807 in 1,239,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. T3I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: ING5 NM_032329.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56
• Publications: 0 publications found

Genes affected

ING5 (HGNC:19421): (inhibitor of growth family member 5) This gene encodes a tumor suppressor protein that inhibits cell growth and induces apoptosis. This protein contains a PHD-type zinc finger. It interacts with tumor suppressor p53 and p300, a component of the histone acetyl transferase complex, suggesting a role in transcriptional regulation. Alternative splicing and the use of multiple promoters and 3' terminal exons results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08541232).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032329.6. 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
	ING5	NM_032329.6	MANE Select	c.8C>G	p.Thr3Ser	missense	Exon 1 of 8	NP_115705.2
	ING5	NM_001330162.2		c.8C>G	p.Thr3Ser	missense	Exon 1 of 8	NP_001317091.1	Q8WYH8-2
	ING5	NM_001330161.2		c.44-2580C>G		intron	N/A	NP_001317090.1	A0A1B0GW41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING5	ENST00000313552.11	TSL:1 MANE Select	c.8C>G	p.Thr3Ser	missense	Exon 1 of 8	ENSP00000322142.7	Q8WYH8-1
	ING5	ENST00000406941.5	TSL:1	c.8C>G	p.Thr3Ser	missense	Exon 1 of 8	ENSP00000385937.1	Q8WYH8-2
	ING5	ENST00000948226.1		c.8C>G	p.Thr3Ser	missense	Exon 1 of 10	ENSP00000618285.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.07e-7 AC: 1 AN: 1239492 Hom.: 0 Cov.: 30 AF XY: 0.00000164 AC XY: 1 AN XY: 611218

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24500

American (AMR) AF: 0.0000522 AC: 1 AN: 19150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20266

East Asian (EAS) AF: 0.00 AC: 0 AN: 25338

South Asian (SAS) AF: 0.00 AC: 0 AN: 63540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5024

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 999550

Other (OTH) AF: 0.00 AC: 0 AN: 49580

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.56	N
PhyloP100		3.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.14		Gain of disorder (P = 0.0543)
MVP		0.33
MPC		0.66
ClinPred		0.65	D
GERP RS		3.2
PromoterAI		-0.49	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.42
Mutation Taster		=44/56	disease causing

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: rs946862250; hg19: chr2-242641488;