Variant chr20-63560030-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037335.2(HELZ2):c.7723C>T(p.Arg2575Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000333 in 1,611,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

HELZ2
NM_001037335.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.329

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14796197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HELZ2	NM_001037335.2 linkuse as main transcript	c.7723C>T	p.Arg2575Trp	missense_variant	19/20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3 linkuse as main transcript	c.6016C>T	p.Arg2006Trp	missense_variant	13/14		NP_208384.3
HELZ2	XM_024452006.2 linkuse as main transcript	c.7807C>T	p.Arg2603Trp	missense_variant	17/18		XP_024307774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELZ2	ENST00000467148.2 linkuse as main transcript	c.7723C>T	p.Arg2575Trp	missense_variant	19/20	1	NM_001037335.2	ENSP00000417401	P1	Q9BYK8-1
HELZ2	ENST00000427522.6 linkuse as main transcript	c.6016C>T	p.Arg2006Trp	missense_variant	13/14	1		ENSP00000393257		Q9BYK8-2
HELZ2	ENST00000478861.1 linkuse as main transcript	n.559+559C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000375

AC:

AN:

247914

Hom.:

AF XY:

0.000453

AC XY:

AN XY:

134696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000301

Gnomad EAS exome

AF:

0.000764

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000482

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000322

AC:

470

AN:

1459224

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

229

AN XY:

725936

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.000345

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000392

Gnomad4 NFE exome

AF:

0.000335

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000440

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000500

Hom.:

Bravo

AF:

0.000374

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000371

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000534

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.7723C>T (p.R2575W) alteration is located in exon 19 (coding exon 18) of the HELZ2 gene. This alteration results from a C to T substitution at nucleotide position 7723, causing the arginine (R) at amino acid position 2575 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

.;D

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.81

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.15

T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

0.90

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0030

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.49

MVP

0.58

MPC

0.71

ClinPred

0.14

GERP RS

2.9

Varity_R

0.24

gMVP

0.33

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