chr7-139604132-G-A

Position:

• chr7-139604132-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000406875.8(HIPK2):​c.2204C>T​(p.Ala735Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HIPK2 ENST00000406875.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.81

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]

LOC105375530 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30176342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIPK2	NM_022740.5	c.2204C>T	p.Ala735Val	missense_variant	10/15	ENST00000406875.8	NP_073577.3
LOC105375530	XR_001745383.2	n.206-9981G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIPK2	ENST00000406875.8	c.2204C>T	p.Ala735Val	missense_variant	10/15	1	NM_022740.5	ENSP00000385571	A2
HIPK2	ENST00000428878.6	c.2123C>T	p.Ala708Val	missense_variant	10/15	1		ENSP00000413724	P4
HIPK2	ENST00000342645.7	c.2183C>T	p.Ala728Val	missense_variant	9/11	5		ENSP00000343108

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Dec 01, 2022

The c.2204C>T (p.A735V) alteration is located in exon (coding exon ) of the HIPK2 gene. This alteration results from a C to T substitution at nucleotide position 2204, causing the alanine (A) at amino acid position 735 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.96	N;N;.
REVEL	Benign	0.20
Sift	Benign	0.17	T;T;.
Sift4G	Benign	0.49	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.38
MutPred		0.28		Loss of disorder (P = 0.162);.;.;
MVP		0.57
MPC		0.49
ClinPred		0.73	D
GERP RS		4.5
Varity_R		0.077
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs1434981969; hg19: chr7-139288878;