chr20-63560549-C-T

Position:

chr20-63560549-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001037335.2(HELZ2):c.7430G>A(p.Arg2477Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,613,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

HELZ2
NM_001037335.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019296527).

BP6

Variant 20-63560549-C-T is Benign according to our data. Variant chr20-63560549-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3283982.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HELZ2	NM_001037335.2 linkuse as main transcript	c.7430G>A	p.Arg2477Gln	missense_variant	17/20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3 linkuse as main transcript	c.5723G>A	p.Arg1908Gln	missense_variant	11/14		NP_208384.3
HELZ2	XM_024452006.2 linkuse as main transcript	c.7514G>A	p.Arg2505Gln	missense_variant	15/18		XP_024307774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELZ2	ENST00000467148.2 linkuse as main transcript	c.7430G>A	p.Arg2477Gln	missense_variant	17/20	1	NM_001037335.2	ENSP00000417401	P1	Q9BYK8-1
HELZ2	ENST00000427522.6 linkuse as main transcript	c.5723G>A	p.Arg1908Gln	missense_variant	11/14	1		ENSP00000393257		Q9BYK8-2
HELZ2	ENST00000478861.1 linkuse as main transcript	n.559+40G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000559

AC:

AN:

250354

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135472

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1460786

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.4

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

1.8

N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0070

B;B

Vest4

0.057

MVP

0.33

MPC

0.20

ClinPred

0.020

GERP RS

1.8

Varity_R

0.016

gMVP

0.15

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