dbSNP rs6790979: WNT5A:c.391+11A>G (chr3-55479303-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003392.7(WNT5A):c.391+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,492,062 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0080 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 9 hom. )

Consequence

WNT5A
NM_003392.7 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.211

Publications

1 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: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 3-55479303-T-C is Benign according to our data. Variant chr3-55479303-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 160314.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00796 (1212/152348) while in subpopulation AFR AF = 0.0273 (1134/41584). AF 95% confidence interval is 0.026. There are 16 homozygotes in GnomAd4. There are 569 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1212 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003392.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WNT5A	NM_003392.7	MANE Select	c.391+11A>G	intron	N/A	NP_003383.4
WNT5A	NM_001256105.1		c.346+11A>G	intron	N/A	NP_001243034.1	P41221-2
WNT5A	NM_001377271.1		c.346+11A>G	intron	N/A	NP_001364200.1	P41221-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WNT5A	ENST00000264634.9	TSL:1 MANE Select	c.391+11A>G	intron	N/A	ENSP00000264634.4	P41221-1
WNT5A	ENST00000474267.5	TSL:5	c.391+11A>G	intron	N/A	ENSP00000417310.1	P41221-1
WNT5A	ENST00000497027.5	TSL:2	c.346+11A>G	intron	N/A	ENSP00000420104.1	P41221-2

Frequencies

GnomAD3 genomes

AF:

0.00794

AC:

1208

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00239

AC:

416

AN:

173972

AF XY:

0.00179

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.000993

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000946

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.000786

AC:

1053

AN:

1339714

Hom.:

Cov.:

AF XY:

0.000676

AC XY:

443

AN XY:

655532

show subpopulations

African (AFR)

AF:

0.0306

AC:

905

AN:

29574

American (AMR)

AF:

0.00138

AC:

AN:

28222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21280

East Asian (EAS)

AF:

0.00

AC:

AN:

37308

South Asian (SAS)

AF:

0.0000629

AC:

AN:

63574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49496

Middle Eastern (MID)

AF:

0.000579

AC:

AN:

5180

European-Non Finnish (NFE)

AF:

0.0000133

AC:

AN:

1050206

Other (OTH)

AF:

0.00160

AC:

AN:

54874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00796

AC:

1212

AN:

152348

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

569

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0273

AC:

1134

AN:

41584

American (AMR)

AF:

0.00366

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68026

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

121

181

242

302

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:

0.00410

Hom.:

Bravo

AF:

0.00924

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Autosomal dominant Robinow syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.8

(source)

DANN

Benign

0.70

PhyloP100

0.21

Mutation Taster

=100/0

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