16-66910277-C-T

Variant names:

• chr16-66910277-C-T
• rs34621310
• NM_004062.4:c.2150G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004062.4(CDH16):​c.2150G>A​(p.Arg717His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,604,458 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R717C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.025 (165 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (146 hom.)
• Consequence: CDH16 NM_004062.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.164
• Publications: 7 publications found

Genes affected

CDH16 (HGNC:1755): (cadherin 16) This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. Mapped to a previously identified cluster of cadherin genes on chromosome 16q22.1, the gene localizes with superfamily members CDH1, CDH3, CDH5, CDH8 and CDH11. The protein consists of an extracellular domain containing 6 cadherin domains, a transmembrane region and a truncated cytoplasmic domain but lacks the prosequence and tripeptide HAV adhesion recognition sequence typical of most classical cadherins. Expression is exclusively in kidney, where the protein functions as the principal mediator of homotypic cellular recognition, playing a role in the morphogenic direction of tissue development. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004127145).
• BP6: Variant 16-66910277-C-T is Benign according to our data. Variant chr16-66910277-C-T is described in ClinVar as Benign. ClinVar VariationId is 784344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004062.4. 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
	CDH16	NM_004062.4	MANE Select	c.2150G>A	p.Arg717His	missense	Exon 15 of 18	NP_004053.1	O75309-1
	CDH16	NM_001204744.2		c.2084G>A	p.Arg695His	missense	Exon 15 of 18	NP_001191673.1	O75309-2
	CDH16	NM_001204745.2		c.2033G>A	p.Arg678His	missense	Exon 15 of 18	NP_001191674.1	O75309-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH16	ENST00000299752.9	TSL:1 MANE Select	c.2150G>A	p.Arg717His	missense	Exon 15 of 18	ENSP00000299752.4	O75309-1
	CDH16	ENST00000394055.7	TSL:1	c.2084G>A	p.Arg695His	missense	Exon 15 of 18	ENSP00000377619.3	O75309-2
	CDH16	ENST00000568632.5	TSL:1	c.1859G>A	p.Arg620His	missense	Exon 14 of 17	ENSP00000455263.1	O75309-3

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3795 AN: 152134 Hom.: 166 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00688 AC: 1673 AN: 243124 AF XY: 0.00471

Gnomad AFR exome AF: 0.0922

Gnomad AMR exome AF: 0.00418

Gnomad ASJ exome AF: 0.000108

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.00304

GnomAD4 exome AF: 0.00245 AC: 3562 AN: 1452206 Hom.: 146 Cov.: 31 AF XY: 0.00213 AC XY: 1536 AN XY: 721468

African (AFR) AF: 0.0881 AC: 2933 AN: 33294

American (AMR) AF: 0.00503 AC: 220 AN: 43732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25356

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39594

South Asian (SAS) AF: 0.000213 AC: 18 AN: 84672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53080

Middle Eastern (MID) AF: 0.00175 AC: 10 AN: 5718

European-Non Finnish (NFE) AF: 0.0000876 AC: 97 AN: 1106772

Other (OTH) AF: 0.00472 AC: 283 AN: 59988

GnomAD4 genome AF: 0.0249 AC: 3795 AN: 152252 Hom.: 165 Cov.: 32 AF XY: 0.0242 AC XY: 1799 AN XY: 74452

African (AFR) AF: 0.0875 AC: 3633 AN: 41516

American (AMR) AF: 0.00784 AC: 120 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68012

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.00602 Hom.: 65

Bravo AF: 0.0291

ESP6500AA AF: 0.0848 AC: 373

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00816 AC: 990

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.16
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.054
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		0.63	P
Vest4		0.16
MVP		0.58
MPC		0.10
ClinPred		0.026	T
GERP RS		3.9
Varity_R		0.058
gMVP		0.36
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34621310; hg19: chr16-66944180;