7-139716979-G-T

Variant names:

• chr7-139716979-G-T
• rs747654281
• NM_022740.5:c.56C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HIPK2 NM_022740.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.36

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26189762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIPK2	NM_022740.5	c.56C>A	p.Thr19Asn	missense_variant	Exon 2 of 15	ENST00000406875.8	NP_073577.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIPK2	ENST00000406875.8	c.56C>A	p.Thr19Asn	missense_variant	Exon 2 of 15	1	NM_022740.5	ENSP00000385571.3
HIPK2	ENST00000428878.6	c.56C>A	p.Thr19Asn	missense_variant	Exon 2 of 15	1		ENSP00000413724.2
HIPK2	ENST00000342645.7	c.35C>A	p.Thr12Asn	missense_variant	Exon 1 of 11	5		ENSP00000343108.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248162 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134926

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 SAS 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: 1 AN: 1459816 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725728

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.58	N;N;.
REVEL	Benign	0.068
Sift	Benign	0.15	T;T;.
Sift4G	Benign	0.17	T;T;T
Polyphen		0.65	P;P;.
Vest4		0.56
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);.;
MVP		0.65
MPC		0.54
ClinPred		0.36	T
GERP RS		4.5
Varity_R		0.14
gMVP		0.26

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: rs747654281; hg19: chr7-139416778;