20-63560324-G-T

Variant names:

• chr20-63560324-G-T
• NM_001037335.2:c.7504C>A

Variant summary

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

The NM_001037335.2(HELZ2):​c.7504C>A​(p.Arg2502Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,816 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: 2.31

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELZ2	NM_001037335.2	c.7504C>A	p.Arg2502Ser	missense_variant	Exon 18 of 20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3	c.5797C>A	p.Arg1933Ser	missense_variant	Exon 12 of 14		NP_208384.3
HELZ2	XM_024452006.2	c.7588C>A	p.Arg2530Ser	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.7504C>A	p.Arg2502Ser	missense_variant	Exon 18 of 20	1	NM_001037335.2	ENSP00000417401.1
HELZ2	ENST00000427522.6	c.5797C>A	p.Arg1933Ser	missense_variant	Exon 12 of 14	1		ENSP00000393257.2
HELZ2	ENST00000478861.1	n.559+265C>A		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399816 Hom.: 0 Cov.: 38 AF XY: 0.00000145 AC XY: 1 AN XY: 691076

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.21e-7

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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	.;D
Eigen	Benign	0.038
Eigen_PC	Benign	0.014
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Uncertain	-0.092	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.57
Sift	Benign	0.032	D;D
Sift4G	Benign	0.36	T;T
Polyphen		0.84	P;P
Vest4		0.54
MutPred		0.49		.;Gain of catalytic residue at Q2506 (P = 0.0369);
MVP		0.58
MPC		0.40
ClinPred		0.63	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: chr20-62191677;