7-139716959-A-T

Position:

• chr7-139716959-A-T

Variant summary

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

The NM_022740.5(HIPK2):​c.76T>A​(p.Cys26Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HIPK2 NM_022740.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

Genes affected

HIPK2 (HGNC:14402): (homeodomain interacting protein kinase 2) This gene encodes a conserved serine/threonine kinase that is a member of the homeodomain-interacting protein kinase family. The encoded protein interacts with homeodomain transcription factors and many other transcription factors such as p53, and can function as both a corepressor and a coactivator depending on the transcription factor and its subcellular localization. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 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/exons	MANE	Protein	UniProt
HIPK2	NM_022740.5	c.76T>A	p.Cys26Ser	missense_variant	2/15	ENST00000406875.8	NP_073577.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIPK2	ENST00000406875.8	c.76T>A	p.Cys26Ser	missense_variant	2/15	1	NM_022740.5	ENSP00000385571	A2
HIPK2	ENST00000428878.6	c.76T>A	p.Cys26Ser	missense_variant	2/15	1		ENSP00000413724	P4
HIPK2	ENST00000342645.7	c.55T>A	p.Cys19Ser	missense_variant	1/11	5		ENSP00000343108

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Nov 21, 2023

The c.76T>A (p.C26S) alteration is located in exon 2 (coding exon 2) of the HIPK2 gene. This alteration results from a T to A substitution at nucleotide position 76, causing the cysteine (C) at amino acid position 26 to be replaced by a serine (S). 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	0.22
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Benign	0.86
DEOGEN2	Uncertain	0.59	D;.;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0057	T
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.2	D;D;.
REVEL	Benign	0.22
Sift	Benign	0.14	T;T;.
Sift4G	Benign	0.54	T;T;T
Polyphen		0.47	P;B;.
Vest4		0.55
MutPred		0.64		Gain of disorder (P = 9e-04);Gain of disorder (P = 9e-04);.;
MVP		0.59
MPC		0.55
ClinPred		0.45	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.17
gMVP		0.54

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: chr7-139416758;