5-88722588-G-C

Variant names:

• chr5-88722588-G-C
• rs200087574
• NM_002397.5:c.*16C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002397.5(MEF2C):​c.*16C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,576,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: MEF2C NM_002397.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.177
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 5-88722588-G-C is Benign according to our data. Variant chr5-88722588-G-C is described in ClinVar as Benign. ClinVar VariationId is 206122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000232 (35/150624) while in subpopulation NFE AF = 0.000442 (30/67862). AF 95% confidence interval is 0.000318. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 35 AD gene.

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.*16C>G		3_prime_UTR	Exon 11 of 11	NP_002388.2
	MEF2C	NM_001193347.1		c.*16C>G		3_prime_UTR	Exon 12 of 12	NP_001180276.1
	MEF2C	NM_001193350.2		c.*16C>G		3_prime_UTR	Exon 11 of 11	NP_001180279.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000504921.7	TSL:1 MANE Select	c.*16C>G		3_prime_UTR	Exon 11 of 11	ENSP00000421925.5
	MEF2C	ENST00000340208.9	TSL:1	c.*16C>G		3_prime_UTR	Exon 12 of 12	ENSP00000340874.5
	MEF2C	ENST00000437473.6	TSL:1	c.*16C>G		3_prime_UTR	Exon 11 of 11	ENSP00000396219.2

Frequencies

GnomAD3 genomes AF: 0.000239 AC: 36 AN: 150520 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000457

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000160 AC: 37 AN: 230666 AF XY: 0.000159

Gnomad AFR exome AF: 0.0000662

Gnomad AMR exome AF: 0.000101

Gnomad ASJ exome AF: 0.000448

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000261

Gnomad OTH exome AF: 0.000188

GnomAD4 exome AF: 0.000185 AC: 264 AN: 1425790 Hom.: 0 Cov.: 32 AF XY: 0.000198 AC XY: 140 AN XY: 706572

African (AFR) AF: 0.0000956 AC: 3 AN: 31368

American (AMR) AF: 0.000131 AC: 5 AN: 38302

Ashkenazi Jewish (ASJ) AF: 0.000320 AC: 8 AN: 25016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39228

South Asian (SAS) AF: 0.00 AC: 0 AN: 82088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52358

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5568

European-Non Finnish (NFE) AF: 0.000221 AC: 242 AN: 1093280

Other (OTH) AF: 0.0000854 AC: 5 AN: 58582

GnomAD4 genome AF: 0.000232 AC: 35 AN: 150624 Hom.: 0 Cov.: 32 AF XY: 0.000259 AC XY: 19 AN XY: 73460

African (AFR) AF: 0.0000246 AC: 1 AN: 40720

American (AMR) AF: 0.000132 AC: 2 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000442 AC: 30 AN: 67862

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.000200

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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: rs200087574; hg19: chr5-88018405;