20-63560216-C-T

Variant names:

• chr20-63560216-C-T
• NM_001037335.2:c.7612G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037335.2(HELZ2):​c.7612G>A​(p.Glu2538Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,405,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E2538Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: HELZ2 NM_001037335.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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]

ACMG classification

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=0.09435013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELZ2	NM_001037335.2	c.7612G>A	p.Glu2538Lys	missense_variant	Exon 18 of 20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3	c.5905G>A	p.Glu1969Lys	missense_variant	Exon 12 of 14		NP_208384.3
HELZ2	XM_024452006.2	c.7696G>A	p.Glu2566Lys	missense_variant	Exon 16 of 18		XP_024307774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELZ2	ENST00000467148.2	c.7612G>A	p.Glu2538Lys	missense_variant	Exon 18 of 20	1	NM_001037335.2	ENSP00000417401.1
HELZ2	ENST00000427522.6	c.5905G>A	p.Glu1969Lys	missense_variant	Exon 12 of 14	1		ENSP00000393257.2
HELZ2	ENST00000478861.1	n.559+373G>A		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1405464 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 695344

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	8.1
DANN	Benign	0.84
DEOGEN2	Benign	0.24	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.52	.;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.15
Sift	Benign	0.48	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.036	B;B
Vest4		0.29
MutPred		0.47		.;Gain of MoRF binding (P = 0.0046);
MVP		0.35
MPC		0.24
ClinPred		0.049	T
GERP RS		0.63
Varity_R		0.029
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62191569;