Genetic Variant HIPK2:p.Ala628Thr (chr7-139614394-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022740.5(HIPK2):c.1882G>A(p.Ala628Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HIPK2
NM_022740.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82

Publications

0 publications found

Variant links:

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]

HIPK2 links:

ENSG00000300163 (HGNC:):

ENSG00000300163 links:

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ACMG classification

Classification was made for transcript

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=0.24046275).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022740.5. 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
	HIPK2	NM_022740.5	MANE Select	c.1882G>A	p.Ala628Thr	missense	Exon 8 of 15	NP_073577.3
	HIPK2	NM_001113239.3		c.1801G>A	p.Ala601Thr	missense	Exon 8 of 15	NP_001106710.1	Q9H2X6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HIPK2	ENST00000406875.8	TSL:1 MANE Select	c.1882G>A	p.Ala628Thr	missense	Exon 8 of 15	ENSP00000385571.3	Q9H2X6-1
HIPK2	ENST00000428878.6	TSL:1	c.1801G>A	p.Ala601Thr	missense	Exon 8 of 15	ENSP00000413724.2	Q9H2X6-3
HIPK2	ENST00000907407.1		c.1801G>A	p.Ala601Thr	missense	Exon 8 of 15	ENSP00000577466.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1424762

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706818

African (AFR)

AF:

0.00

AC:

AN:

32350

American (AMR)

AF:

0.00

AC:

AN:

41274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25280

East Asian (EAS)

AF:

0.00

AC:

AN:

37950

South Asian (SAS)

AF:

0.00

AC:

AN:

81860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089068

Other (OTH)

AF:

0.00

AC:

AN:

58602

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.13

Eigen

Benign

-0.034

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.77

M_CAP

Benign

0.0095

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

PhyloP100

5.8

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.39

REVEL

Benign

0.042

Sift

Benign

0.34

Sift4G

Benign

0.68

Polyphen

0.58

Vest4

0.44

MutPred

0.18

Gain of glycosylation at A628 (P = 0.0105)

MVP

0.70

MPC

0.44

ClinPred

0.47

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.45

Mutation Taster

=46/54

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over