NM_182511.4:c.110C>A

Variant names:

• chr18-72542051-G-T
• NM_182511.4:c.110C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182511.4(CBLN2):​c.110C>A​(p.Ala37Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,318 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CBLN2 NM_182511.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29178315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLN2	NM_182511.4	c.110C>A	p.Ala37Asp	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.110C>A	p.Ala37Asp	missense_variant	Exon 3 of 5	1	NM_182511.4	ENSP00000269503.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432318 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 712782

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.41	.;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.83	.;N
REVEL	Benign	0.24
Sift	Uncertain	0.0060	.;D
Sift4G	Benign	0.10	T;T
Polyphen		0.037	B;B
Vest4		0.20
MutPred		0.45		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.86
MPC		1.7
ClinPred		0.33	T
GERP RS		2.7
Varity_R		0.19
gMVP		0.86

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: chr18-70209286;