rs755682005

Positions:

• chr16-89191897-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004933.3(CDH15):​c.1615+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,559,326 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000065 (2 hom.)
• Consequence: CDH15 NM_004933.3 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0006226
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340

Genes affected

CDH15 (HGNC:1754): (cadherin 15) This gene is a member of the cadherin superfamily of genes, encoding calcium-dependent intercellular adhesion glycoproteins. Cadherins consist of an extracellular domain containing 5 cadherin domains, a transmembrane region, and a conserved cytoplasmic domain. Transcripts from this particular cadherin are expressed in myoblasts and upregulated in myotubule-forming cells. The protein is thought to be essential for the control of morphogenetic processes, specifically myogenesis, and may provide a trigger for terminal muscle cell differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 16-89191897-G-A is Benign according to our data. Variant chr16-89191897-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 210624.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-89191897-G-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH15	NM_004933.3	c.1615+3G>A		splice_donor_region_variant, intron_variant		ENST00000289746.3	NP_004924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH15	ENST00000289746.3	c.1615+3G>A		splice_donor_region_variant, intron_variant		1	NM_004933.3	ENSP00000289746	P1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000175 AC: 27 AN: 154322 Hom.: 0 AF XY: 0.000141 AC XY: 12 AN XY: 85354

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000379

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00173

Gnomad SAS exome AF: 0.000125

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000654 AC: 92 AN: 1407142 Hom.: 2 Cov.: 34 AF XY: 0.0000517 AC XY: 36 AN XY: 696618

Gnomad4 AFR exome AF: 0.000122

Gnomad4 AMR exome AF: 0.0000261

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000795

Gnomad4 SAS exome AF: 0.0000246

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.16e-7

Gnomad4 OTH exome AF: 0.000922

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74404

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00233

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000166

Asia WGS AF: 0.00202 AC: 7 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 05, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00062
dbscSNV1_RF	Benign	0.014
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: rs755682005; hg19: chr16-89258305;