Variant chr20-46177989-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -6.08

Variant links:

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]

CDH22 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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_multiple_submitters_no_conflicts, 2 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
CDH22	NM_021248.3 linkuse as main transcript	c.1872C>T	p.Pro624=	synonymous_variant	11/12	ENST00000537909.4
CDH22	XM_011528994.3 linkuse as main transcript	c.1872C>T	p.Pro624=	synonymous_variant	11/12
CDH22	XM_047440373.1 linkuse as main transcript	c.1632C>T	p.Pro544=	synonymous_variant	9/10
CDH22	XM_024451966.2 linkuse as main transcript	c.1509C>T	p.Pro503=	synonymous_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

AF XY:

0.00803

AC XY:

1088

AN XY:

135558

show subpopulations

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.:

AF XY:

0.00264

AC XY:

1920

AN XY:

727168

show subpopulations

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.:

Cov.:

AF XY:

0.00414

AC XY:

308

AN XY:

74478

show subpopulations

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.:

Bravo

AF:

0.00604

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 20, 2018	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over