NM_182511.4:c.347A>T

Variant names:

• chr18-72541814-T-A
• NM_182511.4:c.347A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182511.4(CBLN2):​c.347A>T​(p.Tyr116Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CBLN2 NM_182511.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54

Genes affected

CBLN2 (HGNC:1544): (cerebellin 2 precursor) Predicted to be involved in maintenance of synapse structure and spontaneous synaptic transmission. Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in extracellular space. Predicted to be active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLN2	NM_182511.4	c.347A>T	p.Tyr116Phe	missense_variant	Exon 3 of 5	ENST00000269503.9	NP_872317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLN2	ENST00000269503.9	c.347A>T	p.Tyr116Phe	missense_variant	Exon 3 of 5	1	NM_182511.4	ENSP00000269503.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.347A>T (p.Y116F) alteration is located in exon 3 (coding exon 1) of the CBLN2 gene. This alteration results from a A to T substitution at nucleotide position 347, causing the tyrosine (Y) at amino acid position 116 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.5	.;N
REVEL	Uncertain	0.31
Sift	Benign	0.11	.;T
Sift4G	Benign	0.35	T;T
Polyphen		1.0	D;D
Vest4		0.60
MutPred		0.44		Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);
MVP		0.61
MPC		1.3
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.34
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-70209049; COSMIC: COSV99504407; COSMIC: COSV99504407;