7-139604131-GG-TC

Variant names:

• chr7-139604131-GG-TC
• NM_022740.5:c.2204_2205delCCinsGA
• HIPK2 p.Ala735Gly

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_022740.5(HIPK2):​c.2204_2205delCCinsGA​(p.Ala735Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A735V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HIPK2 NM_022740.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.81
• Publications: 0 publications found

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]

LOC105375530 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.2204_2205delCCinsGA	p.Ala735Gly	missense	N/A	NP_073577.3
	HIPK2	NM_001113239.3		c.2123_2124delCCinsGA	p.Ala708Gly	missense	N/A	NP_001106710.1	Q9H2X6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIPK2	ENST00000406875.8	TSL:1 MANE Select	c.2204_2205delCCinsGA	p.Ala735Gly	missense	N/A	ENSP00000385571.3	Q9H2X6-1
	HIPK2	ENST00000428878.6	TSL:1	c.2123_2124delCCinsGA	p.Ala708Gly	missense	N/A	ENSP00000413724.2	Q9H2X6-3
	HIPK2	ENST00000907407.1		c.2120_2121delCCinsGA	p.Ala707Gly	missense	N/A	ENSP00000577466.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-139288877;