rs78261372

Variant names:

• chr16-89193490-C-G
• rs78261372
• NM_004933.3:c.1876C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-89193490-C-G
• chr16-89193490-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004933.3(CDH15):​c.1876C>G​(p.Leu626Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L626F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 27)
• Consequence: CDH15 NM_004933.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 2 publications found

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]

CDH15 Gene-Disease associations (from GenCC):

• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal dominant 3

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07490188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH15	NM_004933.3	c.1876C>G	p.Leu626Val	missense_variant	Exon 12 of 14	ENST00000289746.3	NP_004924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH15	ENST00000289746.3	c.1876C>G	p.Leu626Val	missense_variant	Exon 12 of 14	1	NM_004933.3	ENSP00000289746.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.6
DANN	Benign	0.85
DEOGEN2	Benign	0.063	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.54
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.026
Sift	Benign	0.16	T
Sift4G	Benign	0.48	T
Polyphen		0.068	B
Vest4		0.14
MutPred		0.51		Gain of MoRF binding (P = 0.0929);
MVP		0.36
MPC		0.037
ClinPred		0.19	T
GERP RS		-1.0
Varity_R		0.11
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs78261372; hg19: chr16-89259898;