20-46177989-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_021248.3(CDH22):c.1872C>T(p.Pro624=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,614,046 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (104 hom.)
• Consequence: CDH22 NM_021248.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.08

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-46177989-G-A is Benign according to our data. Variant chr20-46177989-G-A is described in ClinVar as [Benign]. Clinvar id is 773919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-6.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.1872C>T	p.Pro624=	synonymous_variant	11/12	ENST00000537909.4
CDH22	XM_011528994.3	c.1872C>T	p.Pro624=	synonymous_variant	11/12
CDH22	XM_047440373.1	c.1632C>T	p.Pro544=	synonymous_variant	9/10
CDH22	XM_024451966.2	c.1509C>T	p.Pro503=	synonymous_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.1872C>T	p.Pro624=	synonymous_variant	11/12	2	NM_021248.3	P1

Frequencies

GnomAD3 genomes AF: 0.00403 AC: 614 AN: 152186 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0642

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00958 AC: 2402 AN: 250700 Hom.: 58 AF XY: 0.00803 AC XY: 1088 AN XY: 135558

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0303

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0693

Gnomad SAS exome AF: 0.00134

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00289 AC: 4219 AN: 1461742 Hom.: 104 Cov.: 32 AF XY: 0.00264 AC XY: 1920 AN XY: 727168

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0290

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0620

Gnomad4 SAS exome AF: 0.00134

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.00401 AC: 611 AN: 152304 Hom.: 9 Cov.: 32 AF XY: 0.00414 AC XY: 308 AN XY: 74478

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0640

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00271 Hom.: 13

Bravo AF: 0.00604

Asia WGS AF: 0.0210 AC: 74 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.7
Dann	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs73598378; hg19: chr20-44806628; COSMIC: COSV64837692;