rs7456421

Positions:

• chr7-139715976-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022740.5(HIPK2):​c.1059C>G​(p.Val353=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,613,590 control chromosomes in the GnomAD database, including 55,700 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 0.36 (13715 hom., cov: 32)
  • Exomes 𝑓: 0.22 (41985 hom.)
• Consequence: HIPK2 NM_022740.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.701 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIPK2	NM_022740.5	c.1059C>G	p.Val353=	synonymous_variant	2/15	ENST00000406875.8	NP_073577.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIPK2	ENST00000406875.8	c.1059C>G	p.Val353=	synonymous_variant	2/15	1	NM_022740.5	ENSP00000385571	A2
HIPK2	ENST00000428878.6	c.1059C>G	p.Val353=	synonymous_variant	2/15	1		ENSP00000413724	P4
HIPK2	ENST00000342645.7	c.1038C>G	p.Val346=	synonymous_variant	1/11	5		ENSP00000343108

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54532 AN: 151904 Hom.: 13664 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.326

GnomAD3 exomes AF: 0.271 AC: 67517 AN: 248870 Hom.: 12649 AF XY: 0.247 AC XY: 33411 AN XY: 135198

Gnomad AFR exome AF: 0.724

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.270

Gnomad SAS exome AF: 0.137

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.242

GnomAD4 exome AF: 0.216 AC: 316266 AN: 1461566 Hom.: 41985 Cov.: 34 AF XY: 0.212 AC XY: 153924 AN XY: 727066

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.359 AC: 54651 AN: 152024 Hom.: 13715 Cov.: 32 AF XY: 0.358 AC XY: 26595 AN XY: 74316

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.327

Alfa AF: 0.221 Hom.: 3481

Bravo AF: 0.393

Asia WGS AF: 0.252 AC: 878 AN: 3478

EpiCase AF: 0.193

EpiControl AF: 0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.2
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs7456421; hg19: chr7-139415775; COSMIC: COSV61225717;