20-46174862-C-T

Position:

• chr20-46174862-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021248.3(CDH22):​c.2131G>A​(p.Gly711Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDH22 NM_021248.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.252

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14242706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH22	NM_021248.3	c.2131G>A	p.Gly711Ser	missense_variant	12/12	ENST00000537909.4	NP_067071.1
CDH22	XM_011528994.3	c.2131G>A	p.Gly711Ser	missense_variant	12/12		XP_011527296.1
CDH22	XM_047440373.1	c.1891G>A	p.Gly631Ser	missense_variant	10/10		XP_047296329.1
CDH22	XM_024451966.2	c.1768G>A	p.Gly590Ser	missense_variant	12/12		XP_024307734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.2131G>A	p.Gly711Ser	missense_variant	12/12	2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.2131G>A (p.G711S) alteration is located in exon 11 (coding exon 11) of the CDH22 gene. This alteration results from a G to A substitution at nucleotide position 2131, causing the glycine (G) at amino acid position 711 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.0
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.33	.;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.12
Sift	Benign	0.18	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.74	P;P
Vest4		0.21
MutPred		0.53		Gain of phosphorylation at G711 (P = 0.0062);Gain of phosphorylation at G711 (P = 0.0062);
MVP		0.43
ClinPred		0.22	T
GERP RS		1.2
Varity_R		0.054
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr20-44803501;