5-88722571-GA-G

Position:

• chr5-88722571-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002397.5(MEF2C):​c.*32del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,225,472 control chromosomes in the GnomAD database, including 4,146 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (3195 hom., cov: 28)
  • Exomes 𝑓: 0.14 (951 hom.)
• Consequence: MEF2C NM_002397.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.815

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-AS2 (HGNC:53115): (MEF2C antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-88722571-GA-G is Benign according to our data. Variant chr5-88722571-GA-G is described in ClinVar as [Benign]. Clinvar id is 1223468.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-88722571-GA-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2C	NM_002397.5	c.*32del		3_prime_UTR_variant	11/11	ENST00000504921.7
MEF2C-AS2	NR_146284.1	n.256-40del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2C	ENST00000504921.7	c.*32del		3_prime_UTR_variant	11/11	1	NM_002397.5
MEF2C-AS2	ENST00000657578.1	n.232-39413del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.171 AC: 23836 AN: 139216 Hom.: 3191 Cov.: 28

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0704

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.136 AC: 147306 AN: 1086222 Hom.: 951 Cov.: 8 AF XY: 0.135 AC XY: 72931 AN XY: 539192

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.0521

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.171 AC: 23864 AN: 139250 Hom.: 3195 Cov.: 28 AF XY: 0.169 AC XY: 11389 AN XY: 67194

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.0999

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0617

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.0886

Gnomad4 OTH AF: 0.152

Bravo AF: 0.171

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

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs56660854; hg19: chr5-88018388;