chr5-88883308-GGAGGAGGAGGAAGA-G

Position:

• chr5-88883308-GGAGGAGGAGGAAGA-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The ENST00000437473.6(MEF2C):​c.-507_-494delTCTTCCTCCTCCTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 27)
• Consequence: MEF2C ENST00000437473.6 5_prime_UTR
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.71

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-AS1 (HGNC:48908): (MEF2C antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-88883308-GGAGGAGGAGGAAGA-G is Pathogenic according to our data. Variant chr5-88883308-GGAGGAGGAGGAAGA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 219247.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2C	XM_047417217.1	c.-507_-494delTCTTCCTCCTCCTC		5_prime_UTR_variant	3/13		XP_047273173.1
MEF2C	XM_047417181.1	c.-507_-494delTCTTCCTCCTCCTC		5_prime_UTR_variant	3/13		XP_047273137.1
MEF2C	XM_047417182.1	c.-510_-497delTCTTCCTCCTCCTC		5_prime_UTR_variant	3/13		XP_047273138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000437473.6	c.-507_-494delTCTTCCTCCTCCTC		5_prime_UTR_variant	1/11	1		ENSP00000396219.2
MEF2C	ENST00000340208.9	c.-143+4180_-143+4193delTCTTCCTCCTCCTC		intron_variant		1		ENSP00000340874.5
MEF2C	ENST00000424173.6	c.-143+4180_-143+4193delTCTTCCTCCTCCTC		intron_variant		1		ENSP00000389610.2

Frequencies

GnomAD3 genomes Cov.: 27

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

GnomAD4 genome Cov.: 27

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Frontotemporal dementia Pathogenic:1

Likely pathogenic, criteria provided, single submitter

in vitro;research

Center for Neuroscience and Cell Biology, University of Coimbra, Portugal

Aug 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1085307051; hg19: chr5-88179125;