Variant rs79267778 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001037335.2(HELZ2):c.5711C>T(p.Thr1904Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,595,312 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.00058 ( 4 hom., cov: 34)

Exomes 𝑓: 0.0010 ( 47 hom. )

Consequence

HELZ2
NM_001037335.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.380

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00736928).

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00105 (1513/1443012) while in subpopulation EAS AF= 0.0371 (1437/38754). AF 95% confidence interval is 0.0355. There are 47 homozygotes in gnomad4_exome. There are 746 alleles in male gnomad4_exome subpopulation. Median coverage is 73. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HELZ2	NM_001037335.2 linkuse as main transcript	c.5711C>T	p.Thr1904Met	missense_variant	9/20	ENST00000467148.2
HELZ2	NM_033405.3 linkuse as main transcript	c.4004C>T	p.Thr1335Met	missense_variant	3/14
HELZ2	XM_024452006.2 linkuse as main transcript	c.5711C>T	p.Thr1904Met	missense_variant	8/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELZ2	ENST00000467148.2 linkuse as main transcript	c.5711C>T	p.Thr1904Met	missense_variant	9/20	1	NM_001037335.2	P1	Q9BYK8-1
HELZ2	ENST00000427522.6 linkuse as main transcript	c.4004C>T	p.Thr1335Met	missense_variant	3/14	1			Q9BYK8-2

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0166

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:

0.000893

AC:

186

AN:

208388

Hom.:

AF XY:

0.000904

AC XY:

104

AN XY:

115006

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000643

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0102

Gnomad SAS exome

AF:

0.000587

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000760

Gnomad OTH exome

AF:

0.000383

GnomAD4 exome

AF:

0.00105

AC:

1513

AN:

1443012

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

746

AN XY:

716554

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000472

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0371

Gnomad4 SAS exome

AF:

0.000465

Gnomad4 FIN exome

AF:

0.0000408

Gnomad4 NFE exome

AF:

0.00000815

Gnomad4 OTH exome

AF:

0.000386

GnomAD4 genome

AF:

0.000584

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0166

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000153

Hom.:

Bravo

AF:

0.000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000896

AC:

107

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.076

.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

2.0

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.12

Sift

Benign

0.080

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.60

P;P

Vest4

0.11

MVP

0.35

MPC

0.62

ClinPred

0.038

GERP RS

-0.21

Varity_R

0.025

gMVP

0.29

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