rs4984390

Variant names:

• chr15-94396279-G-A
• rs4984390
• NM_001385001.1:c.1789-2682G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-94396279-G-A
• chr15-94396279-G-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.1789-2682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,872 control chromosomes in the GnomAD database, including 22,865 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 0.53 (22865 hom., cov: 32)
• Consequence: MCTP2 NM_001385001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCTP2	NM_001385001.1	c.1789-2682G>A		intron_variant	Intron 14 of 22	ENST00000357742.10	NP_001371930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCTP2	ENST00000357742.10	c.1789-2682G>A		intron_variant	Intron 14 of 22	1	NM_001385001.1	ENSP00000350377.4
MCTP2	ENST00000451018.7	c.1789-2682G>A		intron_variant	Intron 13 of 19	1		ENSP00000395109.3
MCTP2	ENST00000557742.1	c.553-2682G>A		intron_variant	Intron 6 of 9	1		ENSP00000454847.1
MCTP2	ENST00000456504.5	n.*1327-2682G>A		intron_variant	Intron 15 of 23	1		ENSP00000388887.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80001 AN: 151754 Hom.: 22865 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.527 AC: 80025 AN: 151872 Hom.: 22865 Cov.: 32 AF XY: 0.526 AC XY: 39059 AN XY: 74228

African (AFR) AF: 0.330 AC: 13668 AN: 41400

American (AMR) AF: 0.509 AC: 7764 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2116 AN: 3466

East Asian (EAS) AF: 0.309 AC: 1597 AN: 5168

South Asian (SAS) AF: 0.401 AC: 1925 AN: 4800

European-Finnish (FIN) AF: 0.707 AC: 7449 AN: 10530

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

European-Non Finnish (NFE) AF: 0.644 AC: 43775 AN: 67932

Other (OTH) AF: 0.528 AC: 1111 AN: 2104

Alfa AF: 0.596 Hom.: 100773

Bravo AF: 0.504

Asia WGS AF: 0.388 AC: 1352 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.5
DANN	Benign	0.48
PhyloP100		0.17
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: rs4984390; hg19: chr15-94939508;