chr6-142772282-TGA-GAG

Variant names:

• chr6-142772282-TGA-GAG
• NM_006734.4:c.2455_2457delTCAinsCTC
• HIVEP2 p.Ser819Leu

Variant summary

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

The NM_006734.4(HIVEP2):​c.2455_2457delTCAinsCTC​(p.Ser819Leu) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HIVEP2 NM_006734.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

HIVEP2 (HGNC:4921): (HIVEP zinc finger 2) This gene encodes a member of a family of closely related, large, zinc finger-containing transcription factors. The encoded protein regulates transcription by binding to regulatory regions of various cellular and viral genes that maybe involved in growth, development and metastasis. The protein contains the ZAS domain comprised of two widely separated regions of zinc finger motifs, a stretch of highly acidic amino acids and a serine/threonine-rich sequence. [provided by RefSeq, Nov 2012]

HIVEP2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 43

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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_006734.4. 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
	HIVEP2	NM_006734.4	MANE Select	c.2455_2457delTCAinsCTC	p.Ser819Leu	missense	N/A	NP_006725.3
	HIVEP2	NM_001438449.1		c.2455_2457delTCAinsCTC	p.Ser819Leu	missense	N/A	NP_001425378.1
	HIVEP2	NM_001438450.1		c.2455_2457delTCAinsCTC	p.Ser819Leu	missense	N/A	NP_001425379.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP2	ENST00000367603.8	TSL:1 MANE Select	c.2455_2457delTCAinsCTC	p.Ser819Leu	missense	N/A	ENSP00000356575.2	P31629
	HIVEP2	ENST00000012134.7	TSL:5	c.2455_2457delTCAinsCTC	p.Ser819Leu	missense	N/A	ENSP00000012134.2	P31629
	HIVEP2	ENST00000367604.6	TSL:5	c.2455_2457delTCAinsCTC	p.Ser819Leu	missense	N/A	ENSP00000356576.1	P31629

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

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: chr6-143093419;