rs7176568

Variant names:

• chr15-94295352-T-C
• rs7176568
• NM_001385001.1:c.-65-2849T>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.-65-2849T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,402 control chromosomes in the GnomAD database, including 7,739 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 0.31 (7739 hom., cov: 31)
• Consequence: MCTP2 NM_001385001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCTP2	NM_001385001.1	c.-65-2849T>C		intron_variant	Intron 1 of 22	ENST00000357742.10	NP_001371930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCTP2	ENST00000357742.10	c.-65-2849T>C		intron_variant	Intron 1 of 22	1	NM_001385001.1	ENSP00000350377.4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47393 AN: 151288 Hom.: 7737 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.313 AC: 47422 AN: 151402 Hom.: 7739 Cov.: 31 AF XY: 0.314 AC XY: 23241 AN XY: 73990

African (AFR) AF: 0.223 AC: 9112 AN: 40946

American (AMR) AF: 0.348 AC: 5312 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3468

East Asian (EAS) AF: 0.434 AC: 2237 AN: 5160

South Asian (SAS) AF: 0.397 AC: 1909 AN: 4810

European-Finnish (FIN) AF: 0.327 AC: 3444 AN: 10530

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23076 AN: 67910

Other (OTH) AF: 0.341 AC: 718 AN: 2108

Alfa AF: 0.332 Hom.: 37603

Bravo AF: 0.309

Asia WGS AF: 0.404 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.31
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7176568; hg19: chr15-94838581;