5-19473658-T-G

Variant names:

• chr5-19473658-T-G
• rs751281107
• NM_004934.5:c.1941A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_004934.5(CDH18):​c.1941A>C​(p.Ser647Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: CDH18 NM_004934.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.78
• Publications: 0 publications found

Genes affected

CDH18 (HGNC:1757): (cadherin 18) This gene encodes a type II classical cadherin from the cadherin superfamily of 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. 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 specifically in the central nervous system and is putatively involved in synaptic adhesion, axon outgrowth and guidance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-19473658-T-G is Benign according to our data. Variant chr5-19473658-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3044783.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.78 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004934.5. 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
	CDH18	NM_004934.5	MANE Select	c.1941A>C	p.Ser647Ser	synonymous	Exon 13 of 13	NP_004925.1	Q13634-1
	CDH18	NM_001291956.3		c.1941A>C	p.Ser647Ser	synonymous	Exon 15 of 15	NP_001278885.1	Q13634-1
	CDH18	NM_001349556.2		c.1941A>C	p.Ser647Ser	synonymous	Exon 14 of 14	NP_001336485.1	Q13634-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	ENST00000382275.6	TSL:1 MANE Select	c.1941A>C	p.Ser647Ser	synonymous	Exon 13 of 13	ENSP00000371710.1	Q13634-1
	CDH18	ENST00000274170.8	TSL:1	c.1941A>C	p.Ser647Ser	synonymous	Exon 11 of 11	ENSP00000274170.3	Q13634-1
	CDH18	ENST00000506372.5	TSL:1	c.*107A>C		3_prime_UTR	Exon 13 of 13	ENSP00000424931.1	D6RER2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461528 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727074

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111794

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CDH18-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.56
PhyloP100		-2.8

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: rs751281107; hg19: chr5-19473767;