Genetic Variant NM_022740.5:c.*4893A>G (chr7-139568034-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022740.5(HIPK2):c.*4893A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,336 control chromosomes in the GnomAD database, including 42,350 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 42297 hom., cov: 32)

Exomes 𝑓: 0.69 ( 53 hom. )

Consequence

HIPK2
NM_022740.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIPK2	NM_022740.5 link	c.*4893A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000406875.8	NP_073577.3	Q9H2X6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIPK2	ENST00000406875.8 link	c.*4893A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_022740.5	ENSP00000385571.3		Q9H2X6-1

Frequencies

GnomAD3 genomes

AF:

0.740

AC:

112474

AN:

151992

Hom.:

42229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.836

Gnomad AMI

AF:

0.713

Gnomad AMR

AF:

0.785

Gnomad ASJ

AF:

0.667

Gnomad EAS

AF:

0.915

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.722

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.755

GnomAD4 exome

AF:

0.690

AC:

156

AN:

226

Hom.:

Cov.:

AF XY:

0.657

AC XY:

117

AN XY:

178

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.789

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.646

AC:

102

AN:

158

Other (OTH)

AF:

0.722

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.740

AC:

112601

AN:

152110

Hom.:

42297

Cov.:

AF XY:

0.746

AC XY:

55468

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.837

AC:

34715

AN:

41490

American (AMR)

AF:

0.786

AC:

12013

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

2313

AN:

3468

East Asian (EAS)

AF:

0.915

AC:

4732

AN:

5174

South Asian (SAS)

AF:

0.809

AC:

3899

AN:

4822

European-Finnish (FIN)

AF:

0.722

AC:

7621

AN:

10556

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44818

AN:

67992

Other (OTH)

AF:

0.757

AC:

1602

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1477

2954

4432

5909

7386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.698

Hom.:

66893

Bravo

AF:

0.750

Asia WGS

AF:

0.876

AC:

3046

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.8

(source)

DANN

Benign

0.80

PhyloP100

1.9

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over