dbSNP rs150429222: HELZ2:p.Val2520Ile (chr20-63560270-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_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. 17/22 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

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 VariationId is 2348347.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037335.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELZ2	NM_001037335.2	MANE Select	c.7558G>A	p.Val2520Ile	missense	Exon 18 of 20	NP_001032412.2	Q9BYK8
	HELZ2	NM_033405.3		c.5851G>A	p.Val1951Ile	missense	Exon 12 of 14	NP_208384.3	Q9BYK8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HELZ2	ENST00000467148.2	TSL:1 MANE Select	c.7558G>A	p.Val2520Ile	missense	Exon 18 of 20	ENSP00000417401.1	A0AAA9XBX5
HELZ2	ENST00000850915.1		c.8299G>A	p.Val2767Ile	missense	Exon 18 of 20	ENSP00000520998.1
HELZ2	ENST00000427522.7		n.6275G>A		non_coding_transcript_exon	Exon 12 of 14

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

GnomAD2 exomes

AF:

0.000396

AC:

AN:

179410

AF XY:

0.000434

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 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

African (AFR)

AF:

0.000154

AC:

AN:

32394

American (AMR)

AF:

0.0000264

AC:

AN:

37928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24962

East Asian (EAS)

AF:

0.00

AC:

AN:

37206

South Asian (SAS)

AF:

0.0000370

AC:

AN:

81006

European-Finnish (FIN)

AF:

0.0000233

AC:

AN:

42970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5190

European-Non Finnish (NFE)

AF:

0.00116

AC:

1260

AN:

1090256

Other (OTH)

AF:

0.000461

AC:

AN:

58568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

148

221

295

369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000434

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000868

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Benign

1.1

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.20

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.68

M_CAP

Benign

0.042

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.81

PhyloP100

1.5

PrimateAI

Benign

0.27

PROVEAN

Benign

0.35

REVEL

Benign

0.22

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.013

Vest4

0.25

MVP

0.33

MPC

0.15

ClinPred

0.016

GERP RS

-1.3

Varity_R

0.0088

gMVP

0.33

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over