rs62620048

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_003392.7(WNT5A):c.*38C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 1,610,436 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 3 hom., cov: 33)

Exomes 𝑓: 0.010 ( 94 hom. )

Consequence

WNT5A
NM_003392.7 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.24

Publications

6 publications found

Variant links:

Genes affected

WNT5A (HGNC:12784): (Wnt family member 5A) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis. Mutations in this gene are the cause of autosomal dominant Robinow syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

WNT5A Gene-Disease associations (from GenCC):

autosomal dominant Robinow syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
autosomal dominant Robinow syndrome
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

WNT5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 3-55470054-G-A is Benign according to our data. Variant chr3-55470054-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 346265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1110 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	NM_003392.7 link	c.*38C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000264634.9	NP_003383.4	P41221-1A0A384N611B3KQX9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT5A	ENST00000264634.9 link	c.*38C>T	3_prime_UTR_variant	Exon 5 of 5	1	NM_003392.7	ENSP00000264634.4	P41221-1
WNT5A	ENST00000493406.1 link	n.88C>T	non_coding_transcript_exon_variant	Exon 1 of 2	4
WNT5A	ENST00000474267.5 link	c.*38C>T	3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000417310.1	P41221-1
WNT5A	ENST00000497027.5 link	c.*38C>T	3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000420104.1	P41221-2

Frequencies

GnomAD3 genomes

AF:

0.00729

AC:

1110

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00694

AC:

1729

AN:

249192

AF XY:

0.00679

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00481

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00760

GnomAD4 exome

AF:

0.00999

AC:

14568

AN:

1458112

Hom.:

Cov.:

AF XY:

0.00979

AC XY:

7105

AN XY:

725650

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

33402

American (AMR)

AF:

0.00514

AC:

230

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0125

AC:

326

AN:

26104

East Asian (EAS)

AF:

0.000126

AC:

AN:

39674

South Asian (SAS)

AF:

0.000732

AC:

AN:

86118

European-Finnish (FIN)

AF:

0.00336

AC:

179

AN:

53224

Middle Eastern (MID)

AF:

0.0141

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0118

AC:

13088

AN:

1108868

Other (OTH)

AF:

0.00861

AC:

519

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

737

1475

2212

2950

3687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.00729

AC:

1110

AN:

152324

Hom.:

Cov.:

AF XY:

0.00652

AC XY:

486

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00216

AC:

AN:

41574

American (AMR)

AF:

0.00706

AC:

108

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0120

AC:

815

AN:

68034

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0101

Hom.:

Bravo

AF:

0.00836

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 28, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over