rs3784639

Variant names:

• chr15-94473640-T-C
• rs3784639
• NM_001385001.1:c.2471-3056T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385001.1(MCTP2):​c.2471-3056T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 152,304 control chromosomes in the GnomAD database, including 221 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 0.039 (221 hom., cov: 33)
• Consequence: MCTP2 NM_001385001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• 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

ENSG00000287950 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCTP2	NM_001385001.1	c.2471-3056T>C		intron_variant	Intron 21 of 22	ENST00000357742.10	NP_001371930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCTP2	ENST00000357742.10	c.2471-3056T>C		intron_variant	Intron 21 of 22	1	NM_001385001.1	ENSP00000350377.4
MCTP2	ENST00000451018.7	c.2306-3056T>C		intron_variant	Intron 18 of 19	1		ENSP00000395109.3
MCTP2	ENST00000456504.5	n.*2009-3056T>C		intron_variant	Intron 22 of 23	1		ENSP00000388887.1
ENSG00000287950	ENST00000658115.1	n.170-15855A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5860 AN: 152186 Hom.: 219 Cov.: 33

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.0713

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00935

Gnomad OTH AF: 0.0339

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

GnomAD4 genome AF: 0.0385 AC: 5868 AN: 152304 Hom.: 221 Cov.: 33 AF XY: 0.0418 AC XY: 3116 AN XY: 74472

African (AFR) AF: 0.0741 AC: 3081 AN: 41556

American (AMR) AF: 0.0198 AC: 303 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3472

East Asian (EAS) AF: 0.0719 AC: 372 AN: 5174

South Asian (SAS) AF: 0.125 AC: 601 AN: 4826

European-Finnish (FIN) AF: 0.0574 AC: 610 AN: 10620

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00936 AC: 637 AN: 68038

Other (OTH) AF: 0.0336 AC: 71 AN: 2114

Alfa AF: 0.0197 Hom.: 96

Bravo AF: 0.0358

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.9
DANN	Benign	0.83
PhyloP100		1.4
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3784639; hg19: chr15-95016869;