rs1490425241

Variant names:

• chr20-63559254-G-C
• rs1490425241
• NM_001037335.2:c.7942C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-63559254-G-C
• chr20-63559254-G-A
• chr20-63559254-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037335.2(HELZ2):​c.7942C>G​(p.Pro2648Ala) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HELZ2 NM_001037335.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.712
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05399975).

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.7942C>G	p.Pro2648Ala	missense	Exon 20 of 20	NP_001032412.2	Q9BYK8
	HELZ2	NM_033405.3		c.6235C>G	p.Pro2079Ala	missense	Exon 14 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.7942C>G	p.Pro2648Ala	missense	Exon 20 of 20	ENSP00000417401.1	A0AAA9XBX5
	HELZ2	ENST00000850915.1		c.8683C>G	p.Pro2895Ala	missense	Exon 20 of 20	ENSP00000520998.1
	HELZ2	ENST00000427522.7		n.6659C>G		non_coding_transcript_exon	Exon 14 of 14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.061
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.054
DANN	Benign	0.71
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.71
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.19
Sift	Benign	0.13	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.047
MutPred		0.27		Loss of glycosylation at P2648 (P = 0.0113)
MVP		0.13
MPC		0.18
ClinPred		0.15	T
GERP RS		-2.2
Varity_R		0.022
gMVP		0.10
Mutation Taster		=100/0	polymorphism

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: rs1490425241; hg19: chr20-62190607;