22-45923007-CC-GA

Variant names:

• chr22-45923007-CC-GA
• NM_058238.3:c.898_899delGGinsTC
• WNT7B p.Gly300Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_058238.3(WNT7B):​c.898_899delGGinsTC​(p.Gly300Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WNT7B NM_058238.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 0 publications found

Genes affected

WNT7B (HGNC:12787): (Wnt family member 7B) This gene is a member of the WNT gene family, which consists of structurally related genes that 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. Among members of the human WNT family, this gene product is most similar to WNT7A protein. [provided by RefSeq, Oct 2008]

WNT7B Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.9927 (below the threshold of 3.09). Trascript score misZ: 1.4346 (below the threshold of 3.09). GenCC associations: The gene is linked to Tourette syndrome, multiple congenital anomalies/dysmorphic syndrome.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058238.3. 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
	WNT7B	NM_058238.3	MANE Select	c.898_899delGGinsTC	p.Gly300Ser	missense	N/A	NP_478679.1	P56706
	WNT7B	NM_001410806.1		c.910_911delGGinsTC	p.Gly304Ser	missense	N/A	NP_001397735.1	A8K0G1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7B	ENST00000339464.9	TSL:1 MANE Select	c.898_899delGGinsTC	p.Gly300Ser	missense	N/A	ENSP00000341032.4	P56706
	WNT7B	ENST00000409496.7	TSL:2	c.910_911delGGinsTC	p.Gly304Ser	missense	N/A	ENSP00000386546.3	A8K0G1
	WNT7B	ENST00000410089.5	TSL:5	c.850_851delGGinsTC	p.Gly284Ser	missense	N/A	ENSP00000386781.1	B8A595

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-46318887;