Variant chr6-142753376-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_006734.4(HIVEP2):c.7072C>T(p.His2358Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HIVEP2
NM_006734.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.767

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HIVEP2. . Gene score misZ 1.8295 (greater than the threshold 3.09). Trascript score misZ 3.809 (greater than threshold 3.09). GenCC has associacion of gene with autosomal dominant non-syndromic intellectual disability, intellectual disability, autosomal dominant 43.

BP4

Computational evidence support a benign effect (MetaRNN=0.067471385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP2	NM_006734.4 linkuse as main transcript	c.7072C>T	p.His2358Tyr	missense_variant	10/10	ENST00000367603.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP2	ENST00000367603.8 linkuse as main transcript	c.7072C>T	p.His2358Tyr	missense_variant	10/10	1	NM_006734.4	P1
	ENST00000437067.1 linkuse as main transcript	n.96-130G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 43

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Nov 01, 2021

This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PS2_MOD, PM2_SUP -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.19

T;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.023

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

.;.;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.067

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

L;L;L

MutationTaster

Benign

0.50

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.044

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.12

MutPred

0.17

Gain of phosphorylation at H2358 (P = 0.0103);Gain of phosphorylation at H2358 (P = 0.0103);Gain of phosphorylation at H2358 (P = 0.0103);

MVP

0.043

MPC

0.22

ClinPred

0.14

GERP RS

4.8

Varity_R

0.052

gMVP

0.22

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over