Variant 20-63559288-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001037335.2(HELZ2):c.7908C>T(p.Ala2636=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 1,592,092 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 62 hom. )

Consequence

HELZ2
NM_001037335.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.319

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 20-63559288-G-A is Benign according to our data. Variant chr20-63559288-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652546.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.319 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HELZ2	NM_001037335.2 linkuse as main transcript	c.7908C>T	p.Ala2636=	synonymous_variant	20/20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3 linkuse as main transcript	c.6201C>T	p.Ala2067=	synonymous_variant	14/14		NP_208384.3
HELZ2	XM_024452006.2 linkuse as main transcript	c.7992C>T	p.Ala2664=	synonymous_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.7908C>T	p.Ala2636=	synonymous_variant	20/20	1	NM_001037335.2	ENSP00000417401	P1	Q9BYK8-1
HELZ2	ENST00000427522.6 linkuse as main transcript	c.6201C>T	p.Ala2067=	synonymous_variant	14/14	1		ENSP00000393257		Q9BYK8-2
HELZ2	ENST00000478861.1 linkuse as main transcript	n.560-353C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00577

AC:

878

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00973

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00620

AC:

1348

AN:

217568

Hom.:

AF XY:

0.00622

AC XY:

734

AN XY:

117990

show subpopulations

Gnomad AFR exome

AF:

0.000973

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00421

Gnomad EAS exome

AF:

0.000490

Gnomad SAS exome

AF:

0.000293

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.00996

Gnomad OTH exome

AF:

0.00610

GnomAD4 exome

AF:

0.00820

AC:

11806

AN:

1439732

Hom.:

Cov.:

AF XY:

0.00808

AC XY:

5768

AN XY:

713474

show subpopulations

Gnomad4 AFR exome

AF:

0.00135

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.000410

Gnomad4 SAS exome

AF:

0.000360

Gnomad4 FIN exome

AF:

0.0134

Gnomad4 NFE exome

AF:

0.00952

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.00577

AC:

879

AN:

152360

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

418

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0128

Gnomad4 NFE

AF:

0.00973

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00840

Hom.:

Bravo

AF:

0.00449

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

HELZ2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.6

DANN

Benign

0.80

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