chr1-1336133-C-T

Variant names:

• chr1-1336133-C-T
• rs377426716
• NM_001330311.2:c.*9G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001330311.2(DVL1):​c.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,571,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: DVL1 NM_001330311.2 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0360
• Publications: 0 publications found

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]

DVL1 Gene-Disease associations (from GenCC):

• autosomal dominant Robinow syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant Robinow syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-1336133-C-T is Benign according to our data. Variant chr1-1336133-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3033799.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 132 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330311.2. 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
	DVL1	NM_001330311.2	MANE Select	c.*9G>A		3_prime_UTR	Exon 15 of 15	NP_001317240.1	O14640-1
	DVL1	NM_004421.3		c.*9G>A		3_prime_UTR	Exon 15 of 15	NP_004412.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DVL1	ENST00000378888.10	TSL:5 MANE Select	c.*9G>A		3_prime_UTR	Exon 15 of 15	ENSP00000368166.5	O14640-1
	DVL1	ENST00000378891.9	TSL:1	c.*9G>A		3_prime_UTR	Exon 15 of 15	ENSP00000368169.5	O14640-2
	DVL1	ENST00000874577.1		c.*9G>A		3_prime_UTR	Exon 15 of 15	ENSP00000544636.1

Frequencies

GnomAD3 genomes AF: 0.000867 AC: 132 AN: 152220 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000221 AC: 41 AN: 185672 AF XY: 0.000128

Gnomad AFR exome AF: 0.00315

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000493

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000705 AC: 100 AN: 1419294 Hom.: 0 Cov.: 31 AF XY: 0.0000597 AC XY: 42 AN XY: 703702

African (AFR) AF: 0.00269 AC: 89 AN: 33038

American (AMR) AF: 0.0000242 AC: 1 AN: 41356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25616

East Asian (EAS) AF: 0.00 AC: 0 AN: 38528

South Asian (SAS) AF: 0.00 AC: 0 AN: 82448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1097846

Other (OTH) AF: 0.000118 AC: 7 AN: 59198

GnomAD4 genome AF: 0.000866 AC: 132 AN: 152338 Hom.: 0 Cov.: 34 AF XY: 0.000819 AC XY: 61 AN XY: 74494

African (AFR) AF: 0.00298 AC: 124 AN: 41584

American (AMR) AF: 0.000457 AC: 7 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00105

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DVL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.71
PhyloP100		-0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs377426716; hg19: chr1-1271513; COSMIC: COSV59563426; COSMIC: COSV59563426;