Genetic Variant HELZ2:p.Met2647Ile (chr20-63559255-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037335.2(HELZ2):c.7941G>A(p.Met2647Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M2647T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HELZ2
NM_001037335.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.24

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.071198046).

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.7941G>A	p.Met2647Ile	missense	Exon 20 of 20	NP_001032412.2	Q9BYK8
	HELZ2	NM_033405.3		c.6234G>A	p.Met2078Ile	missense	Exon 14 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.7941G>A	p.Met2647Ile	missense	Exon 20 of 20	ENSP00000417401.1	A0AAA9XBX5
HELZ2	ENST00000850915.1		c.8682G>A	p.Met2894Ile	missense	Exon 20 of 20	ENSP00000520998.1
HELZ2	ENST00000427522.7		n.6658G>A		non_coding_transcript_exon	Exon 14 of 14

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1413800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697276

African (AFR)

AF:

0.00

AC:

AN:

32960

American (AMR)

AF:

0.00

AC:

AN:

37682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25082

East Asian (EAS)

AF:

0.00

AC:

AN:

38252

South Asian (SAS)

AF:

0.00

AC:

AN:

80916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5088

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085724

Other (OTH)

AF:

0.00

AC:

AN:

58396

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.6

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.014

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.47

M_CAP

Benign

0.026

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.55

PhyloP100

-1.2

PrimateAI

Benign

0.30

PROVEAN

Benign

0.11

REVEL

Benign

0.21

Sift

Benign

0.26

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.13

MutPred

0.29

Loss of helix (P = 0.0376)

MVP

0.37

MPC

0.20

ClinPred

0.058

GERP RS

1.8

Varity_R

0.11

gMVP

0.11

Mutation Taster

=99/1

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over