Genetic Variant NM_022740.5:c.56C>A (chr7-139716979-G-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.56C>A(p.Thr19Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T19I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HIPK2
NM_022740.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.36

Publications

2 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:

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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=0.26189762).

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.56C>A	p.Thr19Asn	missense	Exon 2 of 15	NP_073577.3
	HIPK2	NM_001113239.3		c.56C>A	p.Thr19Asn	missense	Exon 2 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.56C>A	p.Thr19Asn	missense	Exon 2 of 15	ENSP00000385571.3	Q9H2X6-1
HIPK2	ENST00000428878.6	TSL:1	c.56C>A	p.Thr19Asn	missense	Exon 2 of 15	ENSP00000413724.2	Q9H2X6-3
HIPK2	ENST00000907407.1		c.56C>A	p.Thr19Asn	missense	Exon 2 of 15	ENSP00000577466.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248162

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459816

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.0000224

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110272

Other (OTH)

AF:

0.00

AC:

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0044

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

PhyloP100

6.4

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.58

REVEL

Benign

0.068

Sift

Benign

0.15

Sift4G

Benign

0.17

Polyphen

0.65

Vest4

0.56

MutPred

0.17

Gain of relative solvent accessibility (P = 0.0215)

MVP

0.65

MPC

0.54

ClinPred

0.36

GERP RS

4.5

PromoterAI

0.0013

Neutral

(source)

Varity_R

0.14

gMVP

0.26

Mutation Taster

=87/13

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over