Variant chr20-63560524-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001037335.2(HELZ2):c.7455A>T(p.Glu2485Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,602,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

HELZ2
NM_001037335.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.328

Variant links:

Genes affected

HELZ2 (HGNC:30021): (helicase with zinc finger 2) The protein encoded by this gene is a nuclear transcriptional co-activator for peroxisome proliferator activated receptor alpha. The encoded protein contains a zinc finger and is a helicase that appears to be part of the peroxisome proliferator activated receptor alpha interacting complex. This gene is a member of the DNA2/NAM7 helicase gene family. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HELZ2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024270147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HELZ2	NM_001037335.2 linkuse as main transcript	c.7455A>T	p.Glu2485Asp	missense_variant	17/20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3 linkuse as main transcript	c.5748A>T	p.Glu1916Asp	missense_variant	11/14		NP_208384.3
HELZ2	XM_024452006.2 linkuse as main transcript	c.7539A>T	p.Glu2513Asp	missense_variant	15/18		XP_024307774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELZ2	ENST00000467148.2 linkuse as main transcript	c.7455A>T	p.Glu2485Asp	missense_variant	17/20	1	NM_001037335.2	ENSP00000417401	P1	Q9BYK8-1
HELZ2	ENST00000427522.6 linkuse as main transcript	c.5748A>T	p.Glu1916Asp	missense_variant	11/14	1		ENSP00000393257		Q9BYK8-2
HELZ2	ENST00000478861.1 linkuse as main transcript	n.559+65A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000208

AC:

AN:

144258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000217

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

GnomAD3 exomes

AF:

0.0000959

AC:

AN:

250158

Hom.:

AF XY:

0.0000813

AC XY:

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1457846

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000676

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:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000208

AC:

AN:

144258

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000217

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.7455A>T (p.E2485D) alteration is located in exon 17 (coding exon 16) of the HELZ2 gene. This alteration results from a A to T substitution at nucleotide position 7455, causing the glutamic acid (E) at amino acid position 2485 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.39

.;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.71

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.6

.;L

MutationTaster

Benign

0.80

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.14

Sift

Benign

0.18

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.15

B;B

Vest4

0.052

MutPred

0.22

.;Loss of sheet (P = 0.0817);

MVP

0.49

MPC

0.19

ClinPred

0.074

GERP RS

-1.1

Varity_R

0.052

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over