rs12929572

Positions:

• chr16-62018678-A-G
• chr16-62018678-A-T

Variant summary

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

The NM_001796.5(CDH8):​c.252+2474T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,170 control chromosomes in the GnomAD database, including 8,173 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 0.30 (8173 hom., cov: 33)
• Consequence: CDH8 NM_001796.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651

Genes affected

CDH8 (HGNC:1767): (cadherin 8) This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed in brain and is putatively involved in synaptic adhesion, axon outgrowth and guidance. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH8	NM_001796.5	c.252+2474T>C		intron_variant		ENST00000577390.6	NP_001787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH8	ENST00000577390.6	c.252+2474T>C		intron_variant		1	NM_001796.5	ENSP00000462701	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45155 AN: 152054 Hom.: 8178 Cov.: 33

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.297 AC: 45152 AN: 152170 Hom.: 8173 Cov.: 33 AF XY: 0.305 AC XY: 22696 AN XY: 74384

Gnomad4 AFR AF: 0.0988

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.316

Alfa AF: 0.345 Hom.: 16651

Bravo AF: 0.284

Asia WGS AF: 0.509 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.75

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: rs12929572; hg19: chr16-62052582;