rs3810481

Variant names:

• chr20-63562092-G-A
• rs3810481
• NM_001037335.2:c.6509C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037335.2(HELZ2):​c.6509C>T​(p.Thr2170Met) variant causes a missense change. The variant allele was found at a frequency of 0.176 in 1,607,588 control chromosomes in the GnomAD database, including 30,713 homozygotes. In-silico tool predicts 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. T2170A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.14 (2361 hom., cov: 35)
  • Exomes 𝑓: 0.18 (28352 hom.)
• Consequence: HELZ2 NM_001037335.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.38
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021822453).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELZ2	NM_001037335.2	c.6509C>T	p.Thr2170Met	missense_variant	Exon 11 of 20	ENST00000467148.2	NP_001032412.2
HELZ2	NM_033405.3	c.4802C>T	p.Thr1601Met	missense_variant	Exon 5 of 14		NP_208384.3
HELZ2	XM_024452006.2	c.6593C>T	p.Thr2198Met	missense_variant	Exon 9 of 18		XP_024307774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELZ2	ENST00000467148.2	c.6509C>T	p.Thr2170Met	missense_variant	Exon 11 of 20	1	NM_001037335.2	ENSP00000417401.1
HELZ2	ENST00000850915.1	c.7250C>T	p.Thr2417Met	missense_variant	Exon 11 of 20			ENSP00000520998.1
HELZ2	ENST00000427522.7	n.5226C>T		non_coding_transcript_exon_variant	Exon 5 of 14

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21318 AN: 151794 Hom.: 2369 Cov.: 35

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.135

GnomAD2 exomes AF: 0.180 AC: 43810 AN: 243100 AF XY: 0.183

Gnomad AFR exome AF: 0.0271

Gnomad AMR exome AF: 0.0913

Gnomad ASJ exome AF: 0.0891

Gnomad EAS exome AF: 0.587

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.180 AC: 262212 AN: 1455660 Hom.: 28352 Cov.: 56 AF XY: 0.181 AC XY: 131111 AN XY: 724072

African (AFR) AF: 0.0229 AC: 760 AN: 33242

American (AMR) AF: 0.0944 AC: 4199 AN: 44462

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 2307 AN: 25830

East Asian (EAS) AF: 0.587 AC: 23209 AN: 39528

South Asian (SAS) AF: 0.225 AC: 19312 AN: 85990

European-Finnish (FIN) AF: 0.170 AC: 8772 AN: 51728

Middle Eastern (MID) AF: 0.106 AC: 609 AN: 5740

European-Non Finnish (NFE) AF: 0.173 AC: 192266 AN: 1109150

Other (OTH) AF: 0.180 AC: 10778 AN: 59990

GnomAD4 genome AF: 0.140 AC: 21303 AN: 151928 Hom.: 2361 Cov.: 35 AF XY: 0.143 AC XY: 10623 AN XY: 74268

African (AFR) AF: 0.0329 AC: 1366 AN: 41464

American (AMR) AF: 0.106 AC: 1610 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 313 AN: 3472

East Asian (EAS) AF: 0.585 AC: 3006 AN: 5136

South Asian (SAS) AF: 0.242 AC: 1147 AN: 4730

European-Finnish (FIN) AF: 0.176 AC: 1863 AN: 10598

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11523 AN: 67952

Other (OTH) AF: 0.133 AC: 281 AN: 2116

Alfa AF: 0.159 Hom.: 7209

Bravo AF: 0.128

TwinsUK AF: 0.176 AC: 651

ALSPAC AF: 0.184 AC: 708

ESP6500AA AF: 0.0363 AC: 159

ESP6500EA AF: 0.146 AC: 1254

ExAC AF: 0.177 AC: 21309

Asia WGS AF: 0.341 AC: 1188 AN: 3478

EpiCase AF: 0.160

EpiControl AF: 0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	.;D
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	.;M
PhyloP100		5.4
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;D
Vest4		0.14
MPC		0.33
ClinPred		0.071	T
GERP RS		4.1
Varity_R		0.51
gMVP		0.61
Mutation Taster		=66/34	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3810481; hg19: chr20-62193445; COSMIC: COSV71295794; COSMIC: COSV71295794;