chr20-63560270-C-T

Position:

chr20-63560270-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.7558G>A(p.Val2520Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000872 in 1,562,616 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 1 hom. )

Consequence

HELZ2
NM_001037335.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.50

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 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=0.041166365).

BP6

Variant 20-63560270-C-T is Benign according to our data. Variant chr20-63560270-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2348347.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.7558G>A	p.Val2520Ile	missense_variant	18/20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3 linkuse as main transcript	c.5851G>A	p.Val1951Ile	missense_variant	12/14		NP_208384.3
HELZ2	XM_024452006.2 linkuse as main transcript	c.7642G>A	p.Val2548Ile	missense_variant	16/18		XP_024307774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELZ2	ENST00000467148.2 linkuse as main transcript	c.7558G>A	p.Val2520Ile	missense_variant	18/20	1	NM_001037335.2	ENSP00000417401	P1	Q9BYK8-1
HELZ2	ENST00000427522.6 linkuse as main transcript	c.5851G>A	p.Val1951Ile	missense_variant	12/14	1		ENSP00000393257		Q9BYK8-2
HELZ2	ENST00000478861.1 linkuse as main transcript	n.559+319G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.000868

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000396

AC:

AN:

179410

Hom.:

AF XY:

0.000434

AC XY:

AN XY:

96792

show subpopulations

Gnomad AFR exome

AF:

0.0000895

Gnomad AMR exome

AF:

0.0000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000410

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000847

Gnomad OTH exome

AF:

0.000209

GnomAD4 exome

AF:

0.000920

AC:

1297

AN:

1410480

Hom.:

Cov.:

AF XY:

0.000888

AC XY:

620

AN XY:

698144

show subpopulations

Gnomad4 AFR exome

AF:

0.000154

Gnomad4 AMR exome

AF:

0.0000264

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.0000233

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.000461

GnomAD4 genome

AF:

0.000434

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000145

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:

0.000868

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000507

Hom.:

Bravo

AF:

0.000434

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000217

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Sep 15, 2021

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

0.074

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Benign

1.1

DANN

Benign

0.86

DEOGEN2

Benign

0.20

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.81

.;N

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.35

N;N

REVEL

Benign

0.22

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.013

B;B

Vest4

0.25

MVP

0.33

MPC

0.15

ClinPred

0.016

GERP RS

-1.3

Varity_R

0.0088

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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