rs2040862

Positions:

• chr5-138084300-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001300939.2(WNT8A):​c.156+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,613,146 control chromosomes in the GnomAD database, including 22,020 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 0.13 (1572 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20448 hom.)
• Consequence: WNT8A NM_001300939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT8A	NM_001300939.2	c.156+17C>T		intron_variant		ENST00000506684.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT8A	ENST00000506684.6	c.156+17C>T		intron_variant		1	NM_001300939.2
WNT8A	ENST00000398754.1	c.102+17C>T		intron_variant		1		P1
WNT8A	ENST00000504809.5	c.156+17C>T		intron_variant		1
WNT8A	ENST00000361560.6	c.102+17C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20009 AN: 151982 Hom.: 1572 Cov.: 32

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.126

GnomAD3 exomes AF: 0.131 AC: 32523 AN: 248860 Hom.: 2748 AF XY: 0.131 AC XY: 17727 AN XY: 134994

Gnomad AFR exome AF: 0.0694

Gnomad AMR exome AF: 0.0726

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.00134

Gnomad SAS exome AF: 0.0769

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.160 AC: 234338 AN: 1461046 Hom.: 20448 Cov.: 34 AF XY: 0.158 AC XY: 115095 AN XY: 726764

Gnomad4 AFR exome AF: 0.0663

Gnomad4 AMR exome AF: 0.0750

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.00106

Gnomad4 SAS exome AF: 0.0776

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.132 AC: 20010 AN: 152100 Hom.: 1572 Cov.: 32 AF XY: 0.132 AC XY: 9819 AN XY: 74358

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0728

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.125

Alfa AF: 0.159 Hom.: 4158

Bravo AF: 0.120

Asia WGS AF: 0.0410 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.7
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs2040862; hg19: chr5-137419989; COSMIC: COSV64231610;