1-1341659-CCA-CCACA

Variant names:

• chr1-1341659-C-CCA
• rs573517540
• NM_001330311.2:c.605+6_605+7dupTG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001330311.2(DVL1):​c.605+6_605+7dupTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,852 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DVL1 NM_001330311.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DVL1	NM_001330311.2	c.605+6_605+7dupTG		splice_region_variant, intron_variant	Intron 5 of 14	ENST00000378888.10	NP_001317240.1
DVL1	NM_004421.3	c.605+6_605+7dupTG		splice_region_variant, intron_variant	Intron 5 of 14		NP_004412.2
DVL1	XM_005244732.5	c.605+6_605+7dupTG		splice_region_variant, intron_variant	Intron 5 of 15		XP_005244789.1
DVL1	XM_005244733.5	c.605+6_605+7dupTG		splice_region_variant, intron_variant	Intron 5 of 15		XP_005244790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DVL1	ENST00000378888.10	c.605+7_605+8insTG		splice_region_variant, intron_variant	Intron 5 of 14	5	NM_001330311.2	ENSP00000368166.5
DVL1	ENST00000378891.9	c.605+7_605+8insTG		splice_region_variant, intron_variant	Intron 5 of 14	1		ENSP00000368169.5
DVL1	ENST00000472445.1	n.*110_*111insTG		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245932 Hom.: 0 AF XY: 0.00000749 AC XY: 1 AN XY: 133512

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000908

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446852 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 716898

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs573517540; hg19: chr1-1277039;