rs141050437

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.1033A>G(p.Ile345Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,614,114 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I345M) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 49 hom. )

Consequence

HIVEP2
NM_006734.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.241

Publications

10 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:

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=0.0025461614).

BP6

Variant 6-142773706-T-C is Benign according to our data. Variant chr6-142773706-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 658 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.1033A>G	p.Ile345Val	missense	Exon 5 of 10	NP_006725.3
HIVEP2	NM_001438449.1		c.1033A>G	p.Ile345Val	missense	Exon 5 of 10	NP_001425378.1
HIVEP2	NM_001438450.1		c.1033A>G	p.Ile345Val	missense	Exon 6 of 11	NP_001425379.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HIVEP2	ENST00000367603.8	TSL:1 MANE Select	c.1033A>G	p.Ile345Val	missense	Exon 5 of 10	ENSP00000356575.2
HIVEP2	ENST00000012134.7	TSL:5	c.1033A>G	p.Ile345Val	missense	Exon 4 of 9	ENSP00000012134.2
HIVEP2	ENST00000367604.6	TSL:5	c.1033A>G	p.Ile345Val	missense	Exon 5 of 10	ENSP00000356576.1

Frequencies

GnomAD3 genomes

AF:

0.00432

AC:

658

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00372

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00489

AC:

1219

AN:

249520

AF XY:

0.00488

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.000985

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0308

Gnomad NFE exome

AF:

0.00433

Gnomad OTH exome

AF:

0.00313

GnomAD4 exome

AF:

0.00426

AC:

6232

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00410

AC XY:

2981

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.00110

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0292

AC:

1557

AN:

53386

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00396

AC:

4399

AN:

1111974

Other (OTH)

AF:

0.00320

AC:

193

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

372

743

1115

1486

1858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<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:

0.00432

AC:

658

AN:

152292

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000649

AC:

AN:

41576

American (AMR)

AF:

0.00105

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0339

AC:

359

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00372

AC:

253

AN:

68020

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00324

Hom.:

Bravo

AF:

0.00198

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000530

AC:

ESP6500EA

AF:

0.00341

AC:

ExAC

AF:

0.00468

AC:

565

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.8

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.060

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.67

PhyloP100

-0.24

PrimateAI

Benign

0.26

PROVEAN

Benign

0.18

REVEL

Benign

0.034

Sift

Benign

0.51

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.040

MVP

0.043

MPC

0.16

ClinPred

0.0045

GERP RS

-7.5

Varity_R

0.015

gMVP

0.16

Mutation Taster

=100/0

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over