dbSNP rs6596422: WNT8A:p.Ala265Ala (chr5-138090758-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001300939.2(WNT8A):c.795G>A(p.Ala265Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,613,938 control chromosomes in the GnomAD database, including 180,986 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 15206 hom., cov: 32)

Exomes 𝑓: 0.47 ( 165780 hom. )

Consequence

WNT8A
NM_001300939.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.34

Publications

19 publications found

Variant links:

Genes affected

WNT8A (HGNC:12788): (Wnt family member 8A) 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 is a member of the WNT gene family, and may be implicated in development of early embryos as well as germ cell tumors. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2014]

WNT8A links:

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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=-0.77).

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT8A	NM_001300939.2 link	c.795G>A	p.Ala265Ala	synonymous_variant	Exon 5 of 5	ENST00000506684.6	NP_001287868.1	Q9H1J5D6RF47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT8A	ENST00000506684.6 link	c.795G>A	p.Ala265Ala	synonymous_variant	Exon 5 of 5	1	NM_001300939.2	ENSP00000426653.1	D6RF47
WNT8A	ENST00000504809.5 link	c.795G>A	p.Ala265Ala	synonymous_variant	Exon 5 of 6	1		ENSP00000424809.1	D6RF94
WNT8A	ENST00000398754.1 link	c.741G>A	p.Ala247Ala	synonymous_variant	Exon 6 of 6	1		ENSP00000381739.1	Q9H1J5-1
WNT8A	ENST00000361560.6 link	n.741G>A		non_coding_transcript_exon_variant	Exon 6 of 8	1		ENSP00000354726.2	Q9H1J5-2

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66593

AN:

151958

Hom.:

15205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.604

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.469

GnomAD2 exomes

AF:

0.479

AC:

119406

AN:

249230

AF XY:

0.483

show subpopulations

Gnomad AFR exome

AF:

0.329

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.536

Gnomad EAS exome

AF:

0.589

Gnomad FIN exome

AF:

0.479

Gnomad NFE exome

AF:

0.482

Gnomad OTH exome

AF:

0.497

GnomAD4 exome

AF:

0.474

AC:

692667

AN:

1461862

Hom.:

165780

Cov.:

AF XY:

0.476

AC XY:

345867

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.335

AC:

11230

AN:

33480

American (AMR)

AF:

0.438

AC:

19599

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

14032

AN:

26136

East Asian (EAS)

AF:

0.601

AC:

23868

AN:

39700

South Asian (SAS)

AF:

0.497

AC:

42888

AN:

86256

European-Finnish (FIN)

AF:

0.486

AC:

25940

AN:

53408

Middle Eastern (MID)

AF:

0.533

AC:

3076

AN:

5768

European-Non Finnish (NFE)

AF:

0.470

AC:

522953

AN:

1112002

Other (OTH)

AF:

0.482

AC:

29081

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

26211

52422

78633

104844

131055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15548

31096

46644

62192

77740

<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:

0.438

AC:

66621

AN:

152076

Hom.:

15206

Cov.:

AF XY:

0.442

AC XY:

32841

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.328

AC:

13605

AN:

41494

American (AMR)

AF:

0.457

AC:

6979

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1880

AN:

3472

East Asian (EAS)

AF:

0.605

AC:

3122

AN:

5158

South Asian (SAS)

AF:

0.505

AC:

2432

AN:

4814

European-Finnish (FIN)

AF:

0.468

AC:

4953

AN:

10574

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.471

AC:

32019

AN:

67974

Other (OTH)

AF:

0.473

AC:

998

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1900

3801

5701

7602

9502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.466

Hom.:

11679

Bravo

AF:

0.433

Asia WGS

AF:

0.562

AC:

1958

AN:

3478

EpiCase

AF:

0.489

EpiControl

AF:

0.493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.44

(source)

DANN

Benign

0.55

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over