chr15-94418016-A-G

Variant names:

• chr15-94418016-A-G
• rs7176028
• NM_001385001.1:c.2085+15997A>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.2085+15997A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,148 control chromosomes in the GnomAD database, including 1,948 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 0.16 (1948 hom., cov: 32)
• Consequence: MCTP2 NM_001385001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 3 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCTP2	NM_001385001.1	c.2085+15997A>G		intron_variant	Intron 17 of 22	ENST00000357742.10	NP_001371930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCTP2	ENST00000357742.10	c.2085+15997A>G		intron_variant	Intron 17 of 22	1	NM_001385001.1	ENSP00000350377.4
MCTP2	ENST00000451018.7	c.2085+15997A>G		intron_variant	Intron 16 of 19	1		ENSP00000395109.3
MCTP2	ENST00000456504.5	n.*1623+15997A>G		intron_variant	Intron 18 of 23	1		ENSP00000388887.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23951 AN: 152030 Hom.: 1948 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.157 AC: 23948 AN: 152148 Hom.: 1948 Cov.: 32 AF XY: 0.162 AC XY: 12032 AN XY: 74386

African (AFR) AF: 0.153 AC: 6340 AN: 41538

American (AMR) AF: 0.153 AC: 2331 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1397 AN: 5170

South Asian (SAS) AF: 0.205 AC: 989 AN: 4816

European-Finnish (FIN) AF: 0.179 AC: 1902 AN: 10602

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9835 AN: 67976

Other (OTH) AF: 0.170 AC: 358 AN: 2112

Alfa AF: 0.150 Hom.: 3513

Bravo AF: 0.155

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.8
DANN	Benign	0.59
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: rs7176028; hg19: chr15-94961245;