chr1-68098709-CAA-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001002292.4(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 NM_001002292.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.953
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002292.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	NM_001002292.4		c.1553_1554delTT	p.Phe518CysfsTer19	frameshift	Exon 12 of 12	NP_001002292.3	Q5T9L3-2
	GNG12-AS1	NR_040077.1		n.409_410delAA		non_coding_transcript_exon	Exon 4 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	ENST00000354777.6	TSL:1	c.1553_1554delTT	p.Phe518CysfsTer19	frameshift	Exon 12 of 12	ENSP00000346829.2	Q5T9L3-2
	GNG12-AS1	ENST00000413628.5	TSL:2	n.378_379delAA		non_coding_transcript_exon	Exon 4 of 9
	GNG12-AS1	ENST00000420587.5	TSL:2	n.394_395delAA		non_coding_transcript_exon	Exon 4 of 10

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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.95

Splicing

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

Other links and lift over

hg19: chr1-68564392;