chr5-22036142-A-T

Position:

• chr5-22036142-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004061.5(CDH12):​c.231+42304T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CDH12 NM_004061.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH12	NM_004061.5	c.231+42304T>A		intron_variant		ENST00000382254.6	NP_004052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH12	ENST00000382254.6	c.231+42304T>A		intron_variant		1	NM_004061.5	ENSP00000371689	P1
CDH12	ENST00000517378.1	n.689+42304T>A		intron_variant, non_coding_transcript_variant		1
CDH12	ENST00000504376.6	c.231+42304T>A		intron_variant		5		ENSP00000423577	P1
CDH12	ENST00000522262.1	c.231+42304T>A		intron_variant		2		ENSP00000428786

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.9
DANN	Benign	0.70

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: rs4701563; hg19: chr5-22036251;