rs2302904

Positions:

• chr5-31317387-C-A
• chr5-31317387-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH6	NM_004932.4	c.1525C>A	p.Leu509Met	missense_variant	10/12	ENST00000265071.3	NP_004923.1
CDH6	NM_001362435.2	c.1525C>A	p.Leu509Met	missense_variant	10/11		NP_001349364.1
CDH6	XM_011513921.4	c.1525C>A	p.Leu509Met	missense_variant	10/12		XP_011512223.1
CDH6	XM_047416591.1	c.1525C>A	p.Leu509Met	missense_variant	10/12		XP_047272547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH6	ENST00000265071.3	c.1525C>A	p.Leu509Met	missense_variant	10/12	2	NM_004932.4	ENSP00000265071	P1
CDH6	ENST00000514738.5	c.1360C>A	p.Leu454Met	missense_variant	10/11	1		ENSP00000424843
CDH6	ENST00000504835.1	n.93C>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.8	.;L
MutationTaster	Benign	0.020	P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.030	D;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2302904; hg19: chr5-31317494;