rs17730347

Variant names:

• chr15-94453650-A-G
• rs17730347
• NM_001385001.1:c.2251-4487A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-94453650-A-G
• chr15-94453650-A-T

Variant summary

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

The NM_001385001.1(MCTP2):​c.2251-4487A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,230 control chromosomes in the GnomAD database, including 1,780 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 0.15 (1780 hom., cov: 33)
• Consequence: MCTP2 NM_001385001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCTP2	NM_001385001.1	c.2251-4487A>G		intron_variant	Intron 19 of 22	ENST00000357742.10	NP_001371930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCTP2	ENST00000357742.10	c.2251-4487A>G		intron_variant	Intron 19 of 22	1	NM_001385001.1	ENSP00000350377.4
MCTP2	ENST00000451018.7	c.2086-4487A>G		intron_variant	Intron 16 of 19	1		ENSP00000395109.3
MCTP2	ENST00000456504.5	n.*1789-4487A>G		intron_variant	Intron 20 of 23	1		ENSP00000388887.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22499 AN: 152112 Hom.: 1780 Cov.: 33

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.148 AC: 22502 AN: 152230 Hom.: 1780 Cov.: 33 AF XY: 0.153 AC XY: 11372 AN XY: 74410

African (AFR) AF: 0.0987 AC: 4103 AN: 41554

American (AMR) AF: 0.154 AC: 2352 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1503 AN: 5184

South Asian (SAS) AF: 0.209 AC: 1003 AN: 4810

European-Finnish (FIN) AF: 0.180 AC: 1909 AN: 10592

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

European-Non Finnish (NFE) AF: 0.152 AC: 10306 AN: 68002

Other (OTH) AF: 0.171 AC: 362 AN: 2114

Alfa AF: 0.153 Hom.: 822

Bravo AF: 0.144

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.63
PhyloP100		-1.3
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: rs17730347; hg19: chr15-94996879;