15-94471426-T-C

Variant names:

• chr15-94471426-T-C
• rs1424695
• NM_001385001.1:c.2470+984T>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.2470+984T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,054 control chromosomes in the GnomAD database, including 23,953 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 0.56 (23953 hom., cov: 32)
• Consequence: MCTP2 NM_001385001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCTP2	NM_001385001.1	c.2470+984T>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.2470+984T>C		intron_variant	Intron 21 of 22	1	NM_001385001.1	ENSP00000350377.4
MCTP2	ENST00000451018.7	c.2305+984T>C		intron_variant	Intron 18 of 19	1		ENSP00000395109.3
MCTP2	ENST00000456504.5	n.*2008+984T>C		intron_variant	Intron 22 of 23	1		ENSP00000388887.1
ENSG00000287950	ENST00000658115.1	n.170-13641A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84890 AN: 151938 Hom.: 23937 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.559 AC: 84945 AN: 152054 Hom.: 23953 Cov.: 32 AF XY: 0.556 AC XY: 41342 AN XY: 74318

African (AFR) AF: 0.510 AC: 21141 AN: 41468

American (AMR) AF: 0.507 AC: 7738 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1764 AN: 3468

East Asian (EAS) AF: 0.519 AC: 2684 AN: 5174

South Asian (SAS) AF: 0.593 AC: 2863 AN: 4824

European-Finnish (FIN) AF: 0.597 AC: 6313 AN: 10572

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40529 AN: 67960

Other (OTH) AF: 0.563 AC: 1188 AN: 2110

Alfa AF: 0.579 Hom.: 107328

Bravo AF: 0.548

Asia WGS AF: 0.550 AC: 1914 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.83
PhyloP100		0.53
Mutation Taster		=100/0	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: rs1424695; hg19: chr15-95014655;