rs17560407

Positions:

• chr5-88887834-A-G
• chr5-88887834-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001193347.1(MEF2C):​c.-239-236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,234 control chromosomes in the GnomAD database, including 2,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (2861 hom., cov: 33)
• Consequence: MEF2C NM_001193347.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.677

Genes affected

MEF2C (HGNC:6996): (myocyte enhancer factor 2C) This locus encodes a member of the MADS box transcription enhancer factor 2 (MEF2) family of proteins, which play a role in myogenesis. The encoded protein, MEF2 polypeptide C, has both trans-activating and DNA binding activities. This protein may play a role in maintaining the differentiated state of muscle cells. Mutations and deletions at this locus have been associated with severe cognitive disability, stereotypic movements, epilepsy, and cerebral malformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

MEF2C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-88887834-A-G is Benign according to our data. Variant chr5-88887834-A-G is described in ClinVar as [Benign]. Clinvar id is 1249101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2C	NM_001193347.1	c.-239-236T>C		intron_variant			NP_001180276.1
MEF2C	NM_001364329.2	c.-236-236T>C		intron_variant			NP_001351258.1
MEF2C	NM_001364330.2	c.-239-236T>C		intron_variant			NP_001351259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000340208.9	c.-239-236T>C		intron_variant		1		ENSP00000340874.5
MEF2C	ENST00000424173.6	c.-239-236T>C		intron_variant		1		ENSP00000389610.2
MEF2C	ENST00000629612.2	c.-236-236T>C		intron_variant		5		ENSP00000486554.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28181 AN: 152116 Hom.: 2856 Cov.: 33

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.185 AC: 28179 AN: 152234 Hom.: 2861 Cov.: 33 AF XY: 0.182 AC XY: 13581 AN XY: 74428

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.196

Alfa AF: 0.199 Hom.: 650

Bravo AF: 0.177

Asia WGS AF: 0.186 AC: 645 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.77

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: rs17560407; hg19: chr5-88183651;