ENST00000354777.6:c.1553_1554delTT

Variant names:

• chr1-68098709-CAA-C
• ENST00000354777.6:c.1553_1554delTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000354777.6(WLS):​c.1553_1554delTT​(p.Phe518CysfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WLS ENST00000354777.6 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.953

Genes affected

WLS (HGNC:30238): (Wnt ligand secretion mediator) Enables Wnt-protein binding activity and identical protein binding activity. Involved in positive regulation of cell communication and protein transport. Located in several cellular components, including Golgi apparatus; early endosome; and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

GNG12-AS1 (HGNC:43938): (GNG12, DIRAS3 and WLS antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WLS	NM_001002292.4	c.1553_1554delTT	p.Phe518CysfsTer19	frameshift_variant	Exon 12 of 12		NP_001002292.3
WLS	XM_011542191.3	c.1559_1560delTT	p.Phe520CysfsTer19	frameshift_variant	Exon 12 of 12		XP_011540493.1
GNG12-AS1	NR_040077.1	n.409_410delAA		non_coding_transcript_exon_variant	Exon 4 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000354777.6	c.1553_1554delTT	p.Phe518CysfsTer19	frameshift_variant	Exon 12 of 12	1		ENSP00000346829.2
GNG12-AS1	ENST00000413628.5	n.378_379delAA		non_coding_transcript_exon_variant	Exon 4 of 9	2
GNG12-AS1	ENST00000420587.5	n.394_395delAA		non_coding_transcript_exon_variant	Exon 4 of 10	2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

WLS: PM2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-68564392;