5-22466113-C-T

Variant names:

• chr5-22466113-C-T
• rs2260217
• NM_004061.5:c.-428+39157G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004061.5(CDH12):​c.-428+39157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,940 control chromosomes in the GnomAD database, including 14,418 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 (14418 hom., cov: 31)
• Consequence: CDH12 NM_004061.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH12	NM_004061.5	c.-428+39157G>A		intron_variant	Intron 2 of 14	ENST00000382254.6	NP_004052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH12	ENST00000382254.6	c.-428+39157G>A		intron_variant	Intron 2 of 14	1	NM_004061.5	ENSP00000371689.1
CDH12	ENST00000504376.6	c.-333+39157G>A		intron_variant	Intron 2 of 13	5		ENSP00000423577.1
CDH12	ENST00000520668.1	n.392+39157G>A		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65067 AN: 151818 Hom.: 14406 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.522

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: 0.429 AC: 65120 AN: 151940 Hom.: 14418 Cov.: 31 AF XY: 0.429 AC XY: 31858 AN XY: 74240

African (AFR) AF: 0.428 AC: 17709 AN: 41406

American (AMR) AF: 0.607 AC: 9275 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1765 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2364 AN: 5146

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4812

European-Finnish (FIN) AF: 0.337 AC: 3559 AN: 10556

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.398 AC: 27033 AN: 67964

Other (OTH) AF: 0.481 AC: 1015 AN: 2108

Alfa AF: 0.414 Hom.: 2220

Bravo AF: 0.458

Asia WGS AF: 0.409 AC: 1424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs2260217; hg19: chr5-22466222;