NM_004932.4:c.1525C>A

Variant names:

• chr5-31317387-C-A
• rs2302904
• NM_004932.4:c.1525C>A

Variant summary

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

The NM_004932.4(CDH6):​c.1525C>A​(p.Leu509Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDH6 NM_004932.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 21 publications found

Genes affected

CDH6 (HGNC:1765): (cadherin 6) This gene encodes a member of the cadherin superfamily. Cadherins are membrane glycoproteins that mediate homophilic cell-cell adhesion and play critical roles in cell differentiation and morphogenesis. The encoded protein is a type II cadherin and may play a role in kidney development as well as endometrium and placenta formation. Decreased expression of this gene may be associated with tumor growth and metastasis. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004932.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH6	NM_004932.4	MANE Select	c.1525C>A	p.Leu509Met	missense	Exon 10 of 12	NP_004923.1
	CDH6	NM_001362435.2		c.1525C>A	p.Leu509Met	missense	Exon 10 of 11	NP_001349364.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH6	ENST00000265071.3	TSL:2 MANE Select	c.1525C>A	p.Leu509Met	missense	Exon 10 of 12	ENSP00000265071.2
	CDH6	ENST00000514738.5	TSL:1	c.1360C>A	p.Leu454Met	missense	Exon 10 of 11	ENSP00000424843.1
	CDH6	ENST00000899823.1		c.1525C>A	p.Leu509Met	missense	Exon 11 of 13	ENSP00000569882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 41735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.72
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.030	D
Polyphen		0.84	P
Vest4		0.38
MutPred		0.60		Gain of methylation at K514 (P = 0.0632)
MVP		0.44
MPC		1.2
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.43
gMVP		0.45
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2302904; hg19: chr5-31317494;