Variant rs3810481 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001037335.2(HELZ2):c.6509C>T(p.Thr2170Met) variant causes a missense change. The variant allele was found at a frequency of 0.176 in 1,607,588 control chromosomes in the GnomAD database, including 30,713 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 2361 hom., cov: 35)

Exomes 𝑓: 0.18 ( 28352 hom. )

Consequence

HELZ2
NM_001037335.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.38

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021822453).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HELZ2	NM_001037335.2 linkuse as main transcript	c.6509C>T	p.Thr2170Met	missense_variant	11/20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3 linkuse as main transcript	c.4802C>T	p.Thr1601Met	missense_variant	5/14		NP_208384.3
HELZ2	XM_024452006.2 linkuse as main transcript	c.6593C>T	p.Thr2198Met	missense_variant	9/18		XP_024307774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELZ2	ENST00000467148.2 linkuse as main transcript	c.6509C>T	p.Thr2170Met	missense_variant	11/20	1	NM_001037335.2	ENSP00000417401	P1	Q9BYK8-1
HELZ2	ENST00000427522.6 linkuse as main transcript	c.4802C>T	p.Thr1601Met	missense_variant	5/14	1		ENSP00000393257		Q9BYK8-2

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21318

AN:

151794

Hom.:

2369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0901

Gnomad EAS

AF:

0.585

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.180

AC:

43810

AN:

243100

Hom.:

5872

AF XY:

0.183

AC XY:

24336

AN XY:

133226

show subpopulations

Gnomad AFR exome

AF:

0.0271

Gnomad AMR exome

AF:

0.0913

Gnomad ASJ exome

AF:

0.0891

Gnomad EAS exome

AF:

0.587

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.180

AC:

262212

AN:

1455660

Hom.:

28352

Cov.:

AF XY:

0.181

AC XY:

131111

AN XY:

724072

show subpopulations

Gnomad4 AFR exome

AF:

0.0229

Gnomad4 AMR exome

AF:

0.0944

Gnomad4 ASJ exome

AF:

0.0893

Gnomad4 EAS exome

AF:

0.587

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.173

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.140

AC:

21303

AN:

151928

Hom.:

2361

Cov.:

AF XY:

0.143

AC XY:

10623

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.0329

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.0901

Gnomad4 EAS

AF:

0.585

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.161

Hom.:

4711

Bravo

AF:

0.128

TwinsUK

AF:

0.176

AC:

651

ALSPAC

AF:

0.184

AC:

708

ESP6500AA

AF:

0.0363

AC:

159

ESP6500EA

AF:

0.146

AC:

1254

ExAC

AF:

0.177

AC:

21309

Asia WGS

AF:

0.341

AC:

1188

AN:

3478

EpiCase

AF:

0.160

EpiControl

AF:

0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

.;D

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

0.00041

P;P

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;D

Vest4

0.14

MPC

0.33

ClinPred

0.071

GERP RS

4.1

Varity_R

0.51

gMVP

0.61

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over