Genetic Variant HIPK2:c.*4893A>G (chr7-139568034-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 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

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 EAS exome

AF:

0.750

Gnomad4 FIN exome

AF:

0.789

Gnomad4 NFE exome

AF:

0.646

Gnomad4 OTH exome

AF:

0.722

GnomAD4 genome

AF:

0.740

AC:

112601

AN:

152110

Hom.:

42297

Cov.:

AF XY:

0.746

AC XY:

55468

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.837

Gnomad4 AMR

AF:

0.786

Gnomad4 ASJ

AF:

0.667

Gnomad4 EAS

AF:

0.915

Gnomad4 SAS

AF:

0.809

Gnomad4 FIN

AF:

0.722

Gnomad4 NFE

AF:

0.659

Gnomad4 OTH

AF:

0.757

Alfa

AF:

0.705

Hom.:

14589

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

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over