rs117019703

chr6-142753412-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2 BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.08

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PP2: Missense variant where missense usually causes diseases, HIVEP2
• 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 [Likely_benign]. Clinvar id is 445845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 404 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP2	NM_006734.4	c.7036C>T	p.Leu2346Phe	missense_variant	10/10	ENST00000367603.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP2	ENST00000367603.8	c.7036C>T	p.Leu2346Phe	missense_variant	10/10	1	NM_006734.4	P1
	ENST00000437067.1	n.96-94G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 404 AN: 152190 Hom.: 1 Cov.: 32

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

GnomAD3 exomes AF: 0.00268 AC: 661 AN: 246880 Hom.: 2 AF XY: 0.00285 AC XY: 383 AN XY: 134228

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 SAS exome AF: 0.00200

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.: 12 Cov.: 31 AF XY: 0.00374 AC XY: 2722 AN XY: 727104

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00212

Gnomad4 FIN exome AF: 0.00209

Gnomad4 NFE exome AF: 0.00449

Gnomad4 OTH exome AF: 0.00237

GnomAD4 genome AF: 0.00266 AC: 405 AN: 152308 Hom.: 1 Cov.: 32 AF XY: 0.00264 AC XY: 197 AN XY: 74484

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.00442

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00358 Hom.: 1

Bravo AF: 0.00246

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.000507 AC: 2

ESP6500EA AF: 0.00361 AC: 30

ExAC AF: 0.00268 AC: 324

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00290

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 01, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	HIVEP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.0065	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.1	M;M;M
MutationTaster	Benign	0.60	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.63	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.85	P;P;P
Vest4		0.19
MVP		0.068
MPC		0.53
ClinPred		0.019	T
GERP RS		5.8
Varity_R		0.047
gMVP		0.091

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

LitVar

Other links and lift over

dbSNP: rs117019703; hg19: chr6-143074549;