Variant chr20-63559278-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001037335.2(HELZ2):c.7918C>T(p.Arg2640Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 1,586,064 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 33 hom. )

Consequence

HELZ2
NM_001037335.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.922

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064971745).

BP6

Variant 20-63559278-G-A is Benign according to our data. Variant chr20-63559278-G-A is described in ClinVar as [Benign]. Clinvar id is 712818.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HELZ2	NM_001037335.2 linkuse as main transcript	c.7918C>T	p.Arg2640Cys	missense_variant	20/20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3 linkuse as main transcript	c.6211C>T	p.Arg2071Cys	missense_variant	14/14		NP_208384.3
HELZ2	XM_024452006.2 linkuse as main transcript	c.8002C>T	p.Arg2668Cys	missense_variant	18/18		XP_024307774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELZ2	ENST00000467148.2 linkuse as main transcript	c.7918C>T	p.Arg2640Cys	missense_variant	20/20	1	NM_001037335.2	ENSP00000417401	P1	Q9BYK8-1
HELZ2	ENST00000427522.6 linkuse as main transcript	c.6211C>T	p.Arg2071Cys	missense_variant	14/14	1		ENSP00000393257		Q9BYK8-2
HELZ2	ENST00000478861.1 linkuse as main transcript	n.560-343C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

555

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00564

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00360

AC:

758

AN:

210574

Hom.:

AF XY:

0.00355

AC XY:

404

AN XY:

113900

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00331

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.000252

Gnomad SAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.000221

Gnomad NFE exome

AF:

0.00487

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00536

AC:

7687

AN:

1433712

Hom.:

Cov.:

AF XY:

0.00515

AC XY:

3657

AN XY:

709618

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00343

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.000180

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.000531

Gnomad4 NFE exome

AF:

0.00602

Gnomad4 OTH exome

AF:

0.00542

GnomAD4 genome

AF:

0.00364

AC:

554

AN:

152352

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00563

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00517

Hom.:

Bravo

AF:

0.00344

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00373

AC:

ExAC

AF:

0.00307

AC:

369

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 11, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.7

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.59

P;P

Vest4

0.25

MVP

0.47

MPC

0.73

ClinPred

0.039

GERP RS

2.5

Varity_R

0.099

gMVP

0.25

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over