5-138092398-T-G

Variant names:

• chr5-138092398-T-G
• rs2306110
• ENST00000361560.6:n.*462T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000361560.6(WNT8A):​n.*462T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,096 control chromosomes in the GnomAD database, including 15,160 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 (15160 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: WNT8A ENST00000361560.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT8A	NR_125351.2	n.*33T>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT8A	ENST00000361560.6	n.*462T>G		downstream_gene_variant		1		ENSP00000354726.2

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66489 AN: 151978 Hom.: 15159 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.467

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.437 AC: 66515 AN: 152096 Hom.: 15160 Cov.: 33 AF XY: 0.441 AC XY: 32789 AN XY: 74338

African (AFR) AF: 0.326 AC: 13518 AN: 41492

American (AMR) AF: 0.456 AC: 6974 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1864 AN: 3472

East Asian (EAS) AF: 0.604 AC: 3120 AN: 5164

South Asian (SAS) AF: 0.504 AC: 2434 AN: 4828

European-Finnish (FIN) AF: 0.468 AC: 4945 AN: 10556

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.471 AC: 32030 AN: 67980

Other (OTH) AF: 0.470 AC: 993 AN: 2112

Alfa AF: 0.465 Hom.: 5252

Bravo AF: 0.432

Asia WGS AF: 0.561 AC: 1953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs2306110; hg19: chr5-137428087; COSMIC: COSV64230961;