1-1340424-G-T

Position:

• chr1-1340424-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001330311.2(DVL1):​c.685C>A​(p.Arg229=) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DVL1 NM_001330311.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

Genes affected

DVL1 (HGNC:3084): (dishevelled segment polarity protein 1) DVL1, the human homolog of the Drosophila dishevelled gene (dsh) encodes a cytoplasmic phosphoprotein that regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. DVL1 is a candidate gene for neuroblastomatous transformation. The Schwartz-Jampel syndrome and Charcot-Marie-Tooth disease type 2A have been mapped to the same region as DVL1. The phenotypes of these diseases may be consistent with defects which might be expected from aberrant expression of a DVL gene during development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=2.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DVL1	NM_001330311.2	c.685C>A	p.Arg229=	synonymous_variant	6/15	ENST00000378888.10	NP_001317240.1
DVL1	NM_004421.3	c.685C>A	p.Arg229=	synonymous_variant	6/15		NP_004412.2
DVL1	XM_005244732.5	c.685C>A	p.Arg229=	synonymous_variant	6/16		XP_005244789.1
DVL1	XM_005244733.5	c.685C>A	p.Arg229=	synonymous_variant	6/16		XP_005244790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DVL1	ENST00000378888.10	c.685C>A	p.Arg229=	synonymous_variant	6/15	5	NM_001330311.2	ENSP00000368166	P3
DVL1	ENST00000378891.9	c.685C>A	p.Arg229=	synonymous_variant	6/15	1		ENSP00000368169	A1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144365982; hg19: chr1-1275804;