rs2117215

Variant names:

• chr15-94336455-A-G
• rs2117215
• NM_001385001.1:c.638-2835A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

MCTP2 Gene-Disease associations (from GenCC):

• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385001.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCTP2	NM_001385001.1	MANE Select	c.638-2835A>G		intron	N/A	NP_001371930.1
	MCTP2	NM_001385002.1		c.638-2835A>G		intron	N/A	NP_001371931.1
	MCTP2	NM_001385003.1		c.638-2835A>G		intron	N/A	NP_001371932.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCTP2	ENST00000357742.10	TSL:1 MANE Select	c.638-2835A>G		intron	N/A	ENSP00000350377.4
	MCTP2	ENST00000451018.7	TSL:1	c.638-2835A>G		intron	N/A	ENSP00000395109.3
	MCTP2	ENST00000456504.5	TSL:1	n.*176-2835A>G		intron	N/A	ENSP00000388887.1

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

African (AFR) AF: 0.517 AC: 21364 AN: 41356

American (AMR) AF: 0.540 AC: 8262 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1856 AN: 3466

East Asian (EAS) AF: 0.354 AC: 1824 AN: 5156

South Asian (SAS) AF: 0.430 AC: 2069 AN: 4816

European-Finnish (FIN) AF: 0.550 AC: 5794 AN: 10530

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.463 AC: 31481 AN: 67942

Other (OTH) AF: 0.486 AC: 1024 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.54
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2117215; hg19: chr15-94879684; COSMIC: COSV59145261;