rs6131030

chr20-46179347-G-Achr20-46179347-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021248.3(CDH22):c.1664-1150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,998 control chromosomes in the GnomAD database, including 13,432 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13432 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.1664-1150C>T		intron_variant		ENST00000537909.4
CDH22	XM_011528994.3	c.1664-1150C>T		intron_variant
CDH22	XM_024451966.2	c.1301-1150C>T		intron_variant
CDH22	XM_047440373.1	c.1424-1150C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.1664-1150C>T		intron_variant		2	NM_021248.3	P1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63581 AN: 151880 Hom.: 13431 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.418 AC: 63600 AN: 151998 Hom.: 13432 Cov.: 32 AF XY: 0.416 AC XY: 30888 AN XY: 74280

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.442

Alfa AF: 0.406 Hom.: 9593

Bravo AF: 0.433

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.6
Dann	Benign	0.76

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: rs6131030; hg19: chr20-44807986;