6-142753376-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.767

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, HIVEP2
• 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	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	c.7072C>T	p.His2358Tyr	missense_variant	10/10	1	NM_006734.4	P1
	ENST00000437067.1	n.96-130G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727140

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	12
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	D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L;L;L
MutationTaster	Benign	0.50	N;N;N
PrimateAI	Benign	0.34	T
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	T
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.

Other links and lift over

hg19: chr6-143074513;