20-46174887-CCC-ACG

Variant names:

• chr20-46174887-CCC-ACG
• NM_021248.3:c.2104_2106delGGGinsCGT
• CDH22 p.Gly702Arg

Variant summary

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

The NM_021248.3(CDH22):​c.2104_2106delGGGinsCGT​(p.Gly702Arg) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G702E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDH22 NM_021248.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 0 publications found

Genes affected

CDH22 (HGNC:13251): (cadherin 22) This gene is a member of the cadherin superfamily. The gene product is composed of five cadherin repeat domains and a cytoplasmic tail similar to the highly conserved cytoplasmic region of classical cadherins. Expressed predominantly in the brain, this putative calcium-dependent cell adhesion protein may play an important role in morphogenesis and tissue formation in neural and non-neural cells during development and maintenance of the brain and neuroendocrine organs. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021248.3. 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
	CDH22	NM_021248.3	MANE Select	c.2104_2106delGGGinsCGT	p.Gly702Arg	missense	N/A	NP_067071.1	Q9UJ99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH22	ENST00000537909.4	TSL:2 MANE Select	c.2104_2106delGGGinsCGT	p.Gly702Arg	missense	N/A	ENSP00000437790.1	Q9UJ99
	CDH22	ENST00000946368.1		c.2104_2106delGGGinsCGT	p.Gly702Arg	missense	N/A	ENSP00000616427.1
	CDH22	ENST00000946370.1		c.2104_2106delGGGinsCGT	p.Gly702Arg	missense	N/A	ENSP00000616429.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.39

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: chr20-44803526;