rs377556489

Variant names:

• chr20-63560324-G-A
• rs377556489
• NM_001037335.2:c.7504C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-63560324-G-A
• chr20-63560324-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001037335.2(HELZ2):​c.7504C>T​(p.Arg2502Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,552,004 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: HELZ2 NM_001037335.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.7504C>T	p.Arg2502Cys	missense	Exon 18 of 20	NP_001032412.2	Q9BYK8
	HELZ2	NM_033405.3		c.5797C>T	p.Arg1933Cys	missense	Exon 12 of 14	NP_208384.3	Q9BYK8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELZ2	ENST00000467148.2	TSL:1 MANE Select	c.7504C>T	p.Arg2502Cys	missense	Exon 18 of 20	ENSP00000417401.1	A0AAA9XBX5
	HELZ2	ENST00000850915.1		c.8245C>T	p.Arg2749Cys	missense	Exon 18 of 20	ENSP00000520998.1
	HELZ2	ENST00000427522.7		n.6221C>T		non_coding_transcript_exon	Exon 12 of 14

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000703 AC: 13 AN: 184808 AF XY: 0.0000804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000739

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000937

Gnomad NFE exome AF: 0.0000816

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000793 AC: 111 AN: 1399814 Hom.: 0 Cov.: 38 AF XY: 0.0000868 AC XY: 60 AN XY: 691076

African (AFR) AF: 0.00 AC: 0 AN: 32106

American (AMR) AF: 0.0000266 AC: 1 AN: 37562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23168

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38460

South Asian (SAS) AF: 0.0000383 AC: 3 AN: 78428

European-Finnish (FIN) AF: 0.0000241 AC: 1 AN: 41534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4994

European-Non Finnish (NFE) AF: 0.0000884 AC: 96 AN: 1085470

Other (OTH) AF: 0.000155 AC: 9 AN: 58092

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74402

African (AFR) AF: 0.0000241 AC: 1 AN: 41532

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000414 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	0.016
Eigen_PC	Benign	-0.0097
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.3
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.56
Sift	Benign	0.058	T
Sift4G	Benign	0.16	T
Polyphen		0.75	P
Vest4		0.58
MVP		0.55
MPC		0.33
ClinPred		0.56	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.72
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs377556489; hg19: chr20-62191677;