6-142753412-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006734.4(HIVEP2):c.7036C>T(p.Leu2346Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0037 in 1,613,938 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 12 hom. )

Consequence

HIVEP2
NM_006734.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.08

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 43
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HIVEP2 links:

ENSG00000233138 (HGNC:):

ENSG00000233138 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006490886).

BP6

Variant 6-142753412-G-A is Benign according to our data. Variant chr6-142753412-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 405 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HIVEP2	NM_006734.4	MANE Select	c.7036C>T	p.Leu2346Phe	missense	Exon 10 of 10	NP_006725.3
HIVEP2	NM_001438449.1		c.7036C>T	p.Leu2346Phe	missense	Exon 10 of 10	NP_001425378.1
HIVEP2	NM_001438450.1		c.7036C>T	p.Leu2346Phe	missense	Exon 11 of 11	NP_001425379.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HIVEP2	ENST00000367603.8	TSL:1 MANE Select	c.7036C>T	p.Leu2346Phe	missense	Exon 10 of 10	ENSP00000356575.2
HIVEP2	ENST00000012134.7	TSL:5	c.7036C>T	p.Leu2346Phe	missense	Exon 9 of 9	ENSP00000012134.2
HIVEP2	ENST00000367604.6	TSL:5	c.7036C>T	p.Leu2346Phe	missense	Exon 10 of 10	ENSP00000356576.1

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

404

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00442

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00268

AC:

661

AN:

246880

AF XY:

0.00285

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00191

Gnomad EAS exome

AF:

0.0000558

Gnomad FIN exome

AF:

0.00246

Gnomad NFE exome

AF:

0.00404

Gnomad OTH exome

AF:

0.00317

GnomAD4 exome

AF:

0.00380

AC:

5561

AN:

1461630

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

2722

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33478

American (AMR)

AF:

0.00132

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00199

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00212

AC:

183

AN:

86258

European-Finnish (FIN)

AF:

0.00209

AC:

111

AN:

53168

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00449

AC:

4996

AN:

1112010

Other (OTH)

AF:

0.00237

AC:

143

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

335

670

1005

1340

1675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00266

AC:

405

AN:

152308

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

197

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41566

American (AMR)

AF:

0.00131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00339

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00442

AC:

301

AN:

68036

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00370

Hom.:

Bravo

AF:

0.00246

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000507

AC:

ESP6500EA

AF:

0.00361

AC:

ExAC

AF:

0.00268

AC:

324

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00290

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

HIVEP2: BP4, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Sep 01, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0074

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.1

PhyloP100

6.1

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.63

REVEL

Benign

0.13

Sift

Benign

0.20

Sift4G

Benign

0.35

Polyphen

0.85

Vest4

0.19

MVP

0.068

MPC

0.53

ClinPred

0.019

GERP RS

5.8

Varity_R

0.047

gMVP

0.091

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over