rs2551493

Positions:

• chr5-22465713-A-C
• chr5-22465713-A-G
• chr5-22465713-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004061.5(CDH12):​c.-428+39557T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,952 control chromosomes in the GnomAD database, including 14,398 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 0.43 (14398 hom., cov: 31)
• Consequence: CDH12 NM_004061.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.937

Genes affected

CDH12 (HGNC:1751): (cadherin 12) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature cadherin protein. These integral membrane proteins mediate calcium-dependent cell-cell adhesion and 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 histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. This particular cadherin appears to be expressed specifically in the brain and its temporal pattern of expression would be consistent with a role during a critical period of neuronal development, perhaps specifically during synaptogenesis. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH12	NM_004061.5	c.-428+39557T>G		intron_variant		ENST00000382254.6	NP_004052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH12	ENST00000382254.6	c.-428+39557T>G		intron_variant		1	NM_004061.5	ENSP00000371689	P1
CDH12	ENST00000504376.6	c.-333+39557T>G		intron_variant		5		ENSP00000423577	P1
CDH12	ENST00000520668.1	n.392+39557T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65019 AN: 151832 Hom.: 14386 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.428 AC: 65072 AN: 151952 Hom.: 14398 Cov.: 31 AF XY: 0.429 AC XY: 31826 AN XY: 74250

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.481

Alfa AF: 0.314 Hom.: 1074

Bravo AF: 0.458

Asia WGS AF: 0.409 AC: 1423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.0
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs2551493; hg19: chr5-22465822;