chr16-62018678-A-G

Variant names:

• chr16-62018678-A-G
• rs12929572
• NM_001796.5:c.252+2474T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001796.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH8	NM_001796.5	MANE Select	c.252+2474T>C		intron	N/A	NP_001787.2
	CDH8	NM_001410893.1		c.252+2474T>C		intron	N/A	NP_001397822.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH8	ENST00000577390.6	TSL:1 MANE Select	c.252+2474T>C		intron	N/A	ENSP00000462701.1
	CDH8	ENST00000299345.10	TSL:5	c.252+2474T>C		intron	N/A	ENSP00000299345.6
	CDH8	ENST00000577730.5	TSL:5	c.252+2474T>C		intron	N/A	ENSP00000462018.1

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

African (AFR) AF: 0.0988 AC: 4107 AN: 41554

American (AMR) AF: 0.353 AC: 5393 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 869 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3242 AN: 5154

South Asian (SAS) AF: 0.513 AC: 2469 AN: 4814

European-Finnish (FIN) AF: 0.374 AC: 3962 AN: 10598

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24033 AN: 67984

Other (OTH) AF: 0.316 AC: 666 AN: 2108

Alfa AF: 0.337 Hom.: 36542

Bravo AF: 0.284

Asia WGS AF: 0.509 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.75
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12929572; hg19: chr16-62052582;