rs1054280

Variant names:

• chr17-7225408-C-G
• rs1054280
• NM_004422.3:c.*457G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-7225408-C-G
• chr17-7225408-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004422.3(DVL2):​c.*457G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000635 in 315,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: DVL2 NM_004422.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37
• Publications: 5 publications found

Genes affected

DVL2 (HGNC:3086): (dishevelled segment polarity protein 2) This gene encodes a member of the dishevelled (dsh) protein family. The vertebrate dsh proteins have approximately 40% amino acid sequence similarity with Drosophila dsh. This gene encodes a 90-kD protein that undergoes posttranslational phosphorylation to form a 95-kD cytoplasmic protein, which may play a role in the signal transduction pathway mediated by multiple Wnt proteins. The mechanisms of dishevelled function in Wnt signaling are likely to be conserved among metazoans. [provided by RefSeq, Jul 2008]

ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACADVL Gene-Disease associations (from GenCC):

• very long chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004422.3. 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
	DVL2	NM_004422.3	MANE Select	c.*457G>C		3_prime_UTR	Exon 15 of 15	NP_004413.1	O14641
	ACADVL	NM_000018.4	MANE Select	c.*311C>G		downstream_gene	N/A	NP_000009.1	P49748-1
	ACADVL	NM_001270447.2		c.*311C>G		downstream_gene	N/A	NP_001257376.1	P49748-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DVL2	ENST00000005340.10	TSL:1 MANE Select	c.*457G>C		3_prime_UTR	Exon 15 of 15	ENSP00000005340.4	O14641
	DVL2	ENST00000951245.1		c.*457G>C		3_prime_UTR	Exon 15 of 15	ENSP00000621304.1
	DVL2	ENST00000930220.1		c.*457G>C		3_prime_UTR	Exon 15 of 15	ENSP00000600279.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000635 AC: 2 AN: 315072 Hom.: 0 Cov.: 3 AF XY: 0.00000597 AC XY: 1 AN XY: 167478

African (AFR) AF: 0.00 AC: 0 AN: 9372

American (AMR) AF: 0.00 AC: 0 AN: 13230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9402

East Asian (EAS) AF: 0.000112 AC: 2 AN: 17932

South Asian (SAS) AF: 0.00 AC: 0 AN: 41484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1336

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 188698

Other (OTH) AF: 0.00 AC: 0 AN: 17578

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1054280; hg19: chr17-7128727;