20-63559287-C-T

Variant names:

Variant summary

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

The NM_001037335.2(HELZ2):c.7909G>A(p.Gly2637Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000071 in 1,591,660 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

HELZ2
NM_001037335.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.30

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:

Genome browser will be placed here

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=0.02579543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELZ2	NM_001037335.2 link	c.7909G>A	p.Gly2637Ser	missense_variant	Exon 20 of 20	ENST00000467148.2	NP_001032412.2	Q9BYK8-1
HELZ2	NM_033405.3 link	c.6202G>A	p.Gly2068Ser	missense_variant	Exon 14 of 14		NP_208384.3	Q9BYK8-2
HELZ2	XM_024452006.2 link	c.7993G>A	p.Gly2665Ser	missense_variant	Exon 18 of 18		XP_024307774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HELZ2	ENST00000467148.2 link	c.7909G>A	p.Gly2637Ser	missense_variant	Exon 20 of 20	1	NM_001037335.2	ENSP00000417401.1	Q9BYK8-1
HELZ2	ENST00000427522.6 link	c.6202G>A	p.Gly2068Ser	missense_variant	Exon 14 of 14	1		ENSP00000393257.2	Q9BYK8-2
HELZ2	ENST00000478861.1 link	n.560-352G>A		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000416

AC:

AN:

216554

Hom.:

AF XY:

0.0000596

AC XY:

AN XY:

117408

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000246

Gnomad SAS exome

AF:

0.0000735

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000310

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000716

AC:

103

AN:

1439326

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

713206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000231

Gnomad4 SAS exome

AF:

0.0000361

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000763

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 14, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.037

DANN

Benign

0.83

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.026

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-0.20

.;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.49

N;N

REVEL

Benign

0.10

Sift

Benign

0.74

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.011

B;B

Vest4

0.039

MutPred

0.44

.;Gain of disorder (P = 0.0234);

MVP

0.095

MPC

0.17

ClinPred

0.011

GERP RS

-7.0

Varity_R

0.028

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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