15-94298496-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001385001.1(MCTP2):c.231G>A(p.Ser77=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,614,002 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (5 hom.)
• Consequence: MCTP2 NM_001385001.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 15-94298496-G-A is Benign according to our data. Variant chr15-94298496-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 710711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.26 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCTP2	NM_001385001.1	c.231G>A	p.Ser77=	synonymous_variant	2/23	ENST00000357742.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCTP2	ENST00000357742.10	c.231G>A	p.Ser77=	synonymous_variant	2/23	1	NM_001385001.1	P1

Frequencies

GnomAD3 genomes AF: 0.000874 AC: 133 AN: 152112 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000794 AC: 199 AN: 250680 Hom.: 0 AF XY: 0.000760 AC XY: 103 AN XY: 135454

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00108 AC: 1581 AN: 1461772 Hom.: 5 Cov.: 33 AF XY: 0.00105 AC XY: 763 AN XY: 727180

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.00130

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.000874 AC: 133 AN: 152230 Hom.: 0 Cov.: 31 AF XY: 0.000940 AC XY: 70 AN XY: 74442

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000854 Hom.: 0

Bravo AF: 0.000960

EpiCase AF: 0.00164

EpiControl AF: 0.00184

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	1.2
Dann	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs139543198; hg19: chr15-94841725; COSMIC: COSV59148797;