chr1-1336201-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PP3_ModerateBP6_ModerateBS2

The NM_001330311.2(DVL1):c.2029C>T(p.Arg677Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000371 in 1,564,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R677H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

DVL1
NM_001330311.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.21

Publications

0 publications found

Variant links:

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

DVL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.845

BP6

Variant 1-1336201-G-A is Benign according to our data. Variant chr1-1336201-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1357912.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 7 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.2029C>T	p.Arg677Cys	missense	Exon 15 of 15	NP_001317240.1	O14640-1
	DVL1	NM_004421.3		c.1954C>T	p.Arg652Cys	missense	Exon 15 of 15	NP_004412.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DVL1	ENST00000378888.10	TSL:5 MANE Select	c.2029C>T	p.Arg677Cys	missense	Exon 15 of 15	ENSP00000368166.5	O14640-1
DVL1	ENST00000378891.9	TSL:1	c.1954C>T	p.Arg652Cys	missense	Exon 15 of 15	ENSP00000368169.5	O14640-2
DVL1	ENST00000874577.1		c.2194C>T	p.Arg732Cys	missense	Exon 15 of 15	ENSP00000544636.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000301

AC:

AN:

166160

AF XY:

0.0000329

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000581

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000361

AC:

AN:

1412468

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

AN XY:

699626

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

32830

American (AMR)

AF:

0.0000254

AC:

AN:

39394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25486

East Asian (EAS)

AF:

0.00

AC:

AN:

37844

South Asian (SAS)

AF:

0.0000244

AC:

AN:

81870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000375

AC:

AN:

1092584

Other (OTH)

AF:

0.0000340

AC:

AN:

58836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000383

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000862

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.074

MetaRNN

Pathogenic

0.84

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

PhyloP100

5.2

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.81

MVP

0.87

MPC

0.11

ClinPred

0.95

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.67

gMVP

0.74

Mutation Taster

=51/49

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over