Genetic Variant HIPK2:p.Gln1035Gln (chr7-139575149-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_022740.5(HIPK2):c.3105G>A(p.Gln1035Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,594,626 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 11 hom. )

Consequence

HIPK2
NM_022740.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.118

Publications

1 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: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 7-139575149-C-T is Benign according to our data. Variant chr7-139575149-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2658015.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.118 with no splicing effect.

BS2

High AC in GnomAd4 at 392 AD gene.

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.3105G>A	p.Gln1035Gln	synonymous	Exon 14 of 15	NP_073577.3
	HIPK2	NM_001113239.3		c.3024G>A	p.Gln1008Gln	synonymous	Exon 14 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.3105G>A	p.Gln1035Gln	synonymous	Exon 14 of 15	ENSP00000385571.3	Q9H2X6-1
HIPK2	ENST00000428878.6	TSL:1	c.3024G>A	p.Gln1008Gln	synonymous	Exon 14 of 15	ENSP00000413724.2	Q9H2X6-3
HIPK2	ENST00000907407.1		c.3021G>A	p.Gln1007Gln	synonymous	Exon 14 of 15	ENSP00000577466.1

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

392

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00260

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00266

AC:

568

AN:

213568

AF XY:

0.00253

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000130

Gnomad ASJ exome

AF:

0.000324

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0195

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00179

AC:

2584

AN:

1442304

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

1288

AN XY:

715542

show subpopulations

African (AFR)

AF:

0.0000602

AC:

AN:

33206

American (AMR)

AF:

0.000144

AC:

AN:

41802

Ashkenazi Jewish (ASJ)

AF:

0.000195

AC:

AN:

25698

East Asian (EAS)

AF:

0.00

AC:

AN:

38954

South Asian (SAS)

AF:

0.00

AC:

AN:

82878

European-Finnish (FIN)

AF:

0.0194

AC:

998

AN:

51326

Middle Eastern (MID)

AF:

0.000541

AC:

AN:

5550

European-Non Finnish (NFE)

AF:

0.00133

AC:

1472

AN:

1103292

Other (OTH)

AF:

0.00164

AC:

AN:

59598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

137

274

411

548

685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

144

180

<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

AF:

0.00257

AC:

392

AN:

152322

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41576

American (AMR)

AF:

0.0000654

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0192

AC:

204

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00260

AC:

177

AN:

68024

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00316

Hom.:

Bravo

AF:

0.000831

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.9

(source)

DANN

Benign

0.74

PhyloP100

-0.12

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over