5-88722571-GAAA-GAA

Variant names:

• chr5-88722571-GA-G
• rs56660854
• NM_002397.5:c.*32delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002397.5(MEF2C):​c.*32delT 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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 1223468.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002397.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	NM_002397.5	MANE Select	c.*32delT		3_prime_UTR	Exon 11 of 11	NP_002388.2
	MEF2C	NM_001193347.1		c.*32delT		3_prime_UTR	Exon 12 of 12	NP_001180276.1	Q06413-5
	MEF2C	NM_001193350.2		c.*32delT		3_prime_UTR	Exon 11 of 11	NP_001180279.1	Q06413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000504921.7	TSL:1 MANE Select	c.*32delT		3_prime_UTR	Exon 11 of 11	ENSP00000421925.5	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.*32delT		3_prime_UTR	Exon 12 of 12	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000437473.6	TSL:1	c.*32delT		3_prime_UTR	Exon 11 of 11	ENSP00000396219.2	Q06413-1

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

GnomAD2 exomes AF: 0.291 AC: 29977 AN: 103102 AF XY: 0.290

Gnomad AFR exome AF: 0.434

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.190

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.271

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

African (AFR) AF: 0.350 AC: 9379 AN: 26764

American (AMR) AF: 0.117 AC: 3565 AN: 30354

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 2981 AN: 19226

East Asian (EAS) AF: 0.0521 AC: 1508 AN: 28954

South Asian (SAS) AF: 0.109 AC: 7064 AN: 64640

European-Finnish (FIN) AF: 0.196 AC: 7714 AN: 39452

Middle Eastern (MID) AF: 0.130 AC: 551 AN: 4224

European-Non Finnish (NFE) AF: 0.130 AC: 107848 AN: 827288

Other (OTH) AF: 0.148 AC: 6696 AN: 45320

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

African (AFR) AF: 0.378 AC: 14601 AN: 38666

American (AMR) AF: 0.0999 AC: 1386 AN: 13872

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 384 AN: 3292

East Asian (EAS) AF: 0.00251 AC: 12 AN: 4790

South Asian (SAS) AF: 0.0617 AC: 268 AN: 4342

European-Finnish (FIN) AF: 0.148 AC: 1174 AN: 7930

Middle Eastern (MID) AF: 0.0687 AC: 18 AN: 262

European-Non Finnish (NFE) AF: 0.0886 AC: 5612 AN: 63316

Other (OTH) AF: 0.152 AC: 291 AN: 1910

Alfa AF: 0.0336 Hom.: 42

Bravo AF: 0.171

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81
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: rs56660854; hg19: chr5-88018388; COSMIC: COSV60924527; COSMIC: COSV60924527;