5-31317387-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004932.4(CDH6):​c.1525C>T​(p.Leu509Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,538,908 control chromosomes in the GnomAD database, including 216,835 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 0.50 (19833 hom., cov: 32)
  • Exomes 𝑓: 0.53 (197002 hom.)
• Consequence: CDH6 NM_004932.4 synonymous
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

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>T	p.Leu509Leu	synonymous	Exon 10 of 12	NP_004923.1
	CDH6	NM_001362435.2		c.1525C>T	p.Leu509Leu	synonymous	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>T	p.Leu509Leu	synonymous	Exon 10 of 12	ENSP00000265071.2
	CDH6	ENST00000514738.5	TSL:1	c.1360C>T	p.Leu454Leu	synonymous	Exon 10 of 11	ENSP00000424843.1
	CDH6	ENST00000899823.1		c.1525C>T	p.Leu509Leu	synonymous	Exon 11 of 13	ENSP00000569882.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76448 AN: 151926 Hom.: 19812 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.480

GnomAD2 exomes AF: 0.532 AC: 128561 AN: 241780 AF XY: 0.533

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.522

Gnomad ASJ exome AF: 0.539

Gnomad EAS exome AF: 0.521

Gnomad FIN exome AF: 0.660

Gnomad NFE exome AF: 0.541

Gnomad OTH exome AF: 0.525

GnomAD4 exome AF: 0.528 AC: 732308 AN: 1386864 Hom.: 197002 Cov.: 26 AF XY: 0.529 AC XY: 366250 AN XY: 692710

African (AFR) AF: 0.368 AC: 11770 AN: 32026

American (AMR) AF: 0.522 AC: 21861 AN: 41906

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 13592 AN: 25176

East Asian (EAS) AF: 0.546 AC: 21464 AN: 39310

South Asian (SAS) AF: 0.509 AC: 41927 AN: 82336

European-Finnish (FIN) AF: 0.655 AC: 34799 AN: 53168

Middle Eastern (MID) AF: 0.484 AC: 2724 AN: 5626

European-Non Finnish (NFE) AF: 0.528 AC: 554106 AN: 1049564

Other (OTH) AF: 0.521 AC: 30065 AN: 57752

GnomAD4 genome AF: 0.503 AC: 76509 AN: 152044 Hom.: 19833 Cov.: 32 AF XY: 0.509 AC XY: 37833 AN XY: 74316

African (AFR) AF: 0.383 AC: 15866 AN: 41476

American (AMR) AF: 0.526 AC: 8043 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1906 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2705 AN: 5160

South Asian (SAS) AF: 0.481 AC: 2315 AN: 4812

European-Finnish (FIN) AF: 0.654 AC: 6909 AN: 10564

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37218 AN: 67964

Other (OTH) AF: 0.479 AC: 1009 AN: 2108

Alfa AF: 0.526 Hom.: 41735

Bravo AF: 0.489

Asia WGS AF: 0.454 AC: 1575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV54066535;