16-61654007-G-A

Variant names:

• chr16-61654007-G-A
• rs35314742
• NM_001796.5:c.2001C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001796.5(CDH8):​c.2001C>T​(p.Tyr667Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,613,250 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (10 hom.)
• Consequence: CDH8 NM_001796.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.419
• Publications: 2 publications found

Genes affected

CDH8 (HGNC:1767): (cadherin 8) 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. This particular cadherin is expressed in brain and is putatively involved in synaptic adhesion, axon outgrowth and guidance. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 16-61654007-G-A is Benign according to our data. Variant chr16-61654007-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 777480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.419 with no splicing effect.
• BS2: High AC in GnomAd4 at 247 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001796.5. 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
	CDH8	NM_001796.5	MANE Select	c.2001C>T	p.Tyr667Tyr	synonymous	Exon 12 of 12	NP_001787.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH8	ENST00000577390.6	TSL:1 MANE Select	c.2001C>T	p.Tyr667Tyr	synonymous	Exon 12 of 12	ENSP00000462701.1	P55286
	CDH8	ENST00000958085.1		c.2001C>T	p.Tyr667Tyr	synonymous	Exon 12 of 12	ENSP00000628144.1
	CDH8	ENST00000299345.10	TSL:5	c.2001C>T	p.Tyr667Tyr	synonymous	Exon 12 of 13	ENSP00000299345.6	X6R3Y6

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 247 AN: 151974 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000853

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00288

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00184 AC: 463 AN: 251386 AF XY: 0.00197

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00285

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00234 AC: 3424 AN: 1461158 Hom.: 10 Cov.: 33 AF XY: 0.00234 AC XY: 1703 AN XY: 726934

African (AFR) AF: 0.000120 AC: 4 AN: 33462

American (AMR) AF: 0.00116 AC: 52 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00195 AC: 168 AN: 86238

European-Finnish (FIN) AF: 0.000505 AC: 27 AN: 53416

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.00275 AC: 3053 AN: 1111360

Other (OTH) AF: 0.00176 AC: 106 AN: 60366

GnomAD4 genome AF: 0.00162 AC: 247 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.00159 AC XY: 118 AN XY: 74314

African (AFR) AF: 0.000602 AC: 25 AN: 41498

American (AMR) AF: 0.000852 AC: 13 AN: 15256

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4814

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10552

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

European-Non Finnish (NFE) AF: 0.00288 AC: 196 AN: 68020

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00256 Hom.: 1

Bravo AF: 0.00158

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00255

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		-0.42
Mutation Taster		=87/13	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: rs35314742; hg19: chr16-61687911; COSMIC: COSV54881869; COSMIC: COSV54881869;