rs2117215

chr15-94336455-A-G

Variant summary

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

The NM_001385001.1(MCTP2):c.638-2835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,854 control chromosomes in the GnomAD database, including 18,225 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 0.49 (18225 hom., cov: 31)
• Consequence: MCTP2 NM_001385001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

Genes affected

MCTP2 (HGNC:25636): (multiple C2 and transmembrane domain containing 2) Enables calcium ion binding activity. Predicted to be involved in regulation of neurotransmitter secretion. Located in cytosol and nucleoplasm. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCTP2	NM_001385001.1	c.638-2835A>G		intron_variant		ENST00000357742.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCTP2	ENST00000357742.10	c.638-2835A>G		intron_variant		1	NM_001385001.1	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74153 AN: 151736 Hom.: 18202 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.489 AC: 74225 AN: 151854 Hom.: 18225 Cov.: 31 AF XY: 0.492 AC XY: 36490 AN XY: 74202

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.486

Alfa AF: 0.472 Hom.: 2135

Bravo AF: 0.493

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.8
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2117215; hg19: chr15-94879684; COSMIC: COSV59145261;