rs6032754

Positions:

• chr20-46290120-T-C
• chr20-46290120-T-G

Variant summary

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

The NM_021248.3(CDH22):​c.-400+18135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,020 control chromosomes in the GnomAD database, including 10,481 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 0.35 (10481 hom., cov: 33)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.-400+18135A>G		intron_variant		ENST00000537909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.-400+18135A>G		intron_variant		2	NM_021248.3	P1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53022 AN: 151902 Hom.: 10460 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.349 AC: 53084 AN: 152020 Hom.: 10481 Cov.: 33 AF XY: 0.352 AC XY: 26146 AN XY: 74316

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.323

Alfa AF: 0.275 Hom.: 12216

Bravo AF: 0.357

Asia WGS AF: 0.272 AC: 946 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.034
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6032754; hg19: chr20-44918759;