Genetic Variant NM_006734.4:c.7299G>A (chr6-142753149-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_006734.4(HIVEP2):c.7299G>A(p.Glu2433Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HIVEP2
NM_006734.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.65

Publications

0 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: Illumina, Labcorp Genetics (formerly Invitae), 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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 6-142753149-C-T is Benign according to our data. Variant chr6-142753149-C-T is described in ClinVar as Benign. ClinVar VariationId is 2077467.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.65 with no splicing effect.

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.7299G>A	p.Glu2433Glu	synonymous	Exon 10 of 10	NP_006725.3
HIVEP2	NM_001438449.1		c.7299G>A	p.Glu2433Glu	synonymous	Exon 10 of 10	NP_001425378.1
HIVEP2	NM_001438450.1		c.7299G>A	p.Glu2433Glu	synonymous	Exon 11 of 11	NP_001425379.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HIVEP2	ENST00000367603.8	TSL:1 MANE Select	c.7299G>A	p.Glu2433Glu	synonymous	Exon 10 of 10	ENSP00000356575.2	P31629
HIVEP2	ENST00000012134.7	TSL:5	c.7299G>A	p.Glu2433Glu	synonymous	Exon 9 of 9	ENSP00000012134.2	P31629
HIVEP2	ENST00000367604.6	TSL:5	c.7299G>A	p.Glu2433Glu	synonymous	Exon 10 of 10	ENSP00000356576.1	P31629

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000802

AC:

AN:

249390

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460478

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726644

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.0000671

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110720

Other (OTH)

AF:

0.00

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.5

(source)

DANN

Benign

0.82

PhyloP100

2.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over