5-26881188-C-G

Variant names:

• chr5-26881188-C-G
• rs553402369
• NM_016279.4:c.2318G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_016279.4(CDH9):​c.2318G>C​(p.Arg773Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,500 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R773L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: CDH9 NM_016279.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34
• Publications: 1 publications found

Genes affected

CDH9 (HGNC:1768): (cadherin 9) This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 25 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016279.4. 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
	CDH9	NM_016279.4	MANE Select	c.2318G>C	p.Arg773Pro	missense	Exon 12 of 12	NP_057363.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH9	ENST00000231021.9	TSL:1 MANE Select	c.2318G>C	p.Arg773Pro	missense	Exon 12 of 12	ENSP00000231021.4	Q9ULB4
	CDH9	ENST00000505020.1	TSL:2	n.1334G>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151946 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1460554 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 726600

African (AFR) AF: 0.0000299 AC: 1 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111256

Other (OTH) AF: 0.0000166 AC: 1 AN: 60318

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151946 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74190

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.026	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.73
Sift	Benign	0.044	D
Sift4G	Uncertain	0.030	D
Polyphen		0.33	B
Vest4		0.41
MutPred		0.82		Gain of catalytic residue at R773 (P = 0.0128)
MVP		0.92
MPC		1.4
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.78
gMVP		0.88
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs553402369; hg19: chr5-26881297;