rs79455305

Variant names:

• chr5-88731897-G-A
• rs79455305
• NM_002397.5:c.642C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-88731897-G-A
• chr5-88731897-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_002397.5(MEF2C):​c.642C>T​(p.Asn214Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,606,346 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (3 hom.)
• Consequence: MEF2C NM_002397.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.185
• Publications: 4 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 5-88731897-G-A is Benign according to our data. Variant chr5-88731897-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.185 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000184 (28/152168) while in subpopulation EAS AF = 0.00464 (24/5176). AF 95% confidence interval is 0.0032. There are 0 homozygotes in GnomAd4. There are 16 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 28 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.642C>T	p.Asn214Asn	synonymous	Exon 7 of 11	NP_002388.2
	MEF2C	NM_001193347.1		c.696C>T	p.Asn232Asn	synonymous	Exon 9 of 12	NP_001180276.1	Q06413-5
	MEF2C	NM_001193350.2		c.642C>T	p.Asn214Asn	synonymous	Exon 7 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.642C>T	p.Asn214Asn	synonymous	Exon 7 of 11	ENSP00000421925.5	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.696C>T	p.Asn232Asn	synonymous	Exon 9 of 12	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000437473.6	TSL:1	c.642C>T	p.Asn214Asn	synonymous	Exon 7 of 11	ENSP00000396219.2	Q06413-1

Frequencies

GnomAD3 genomes AF: 0.000178 AC: 27 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000461 AC: 113 AN: 245180 AF XY: 0.000481

Gnomad AFR exome AF: 0.0000652

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00589

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000241 AC: 351 AN: 1454178 Hom.: 3 Cov.: 31 AF XY: 0.000256 AC XY: 185 AN XY: 722380

African (AFR) AF: 0.0000301 AC: 1 AN: 33184

American (AMR) AF: 0.00 AC: 0 AN: 43870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25912

East Asian (EAS) AF: 0.00768 AC: 304 AN: 39560

South Asian (SAS) AF: 0.000246 AC: 21 AN: 85268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107428

Other (OTH) AF: 0.000383 AC: 23 AN: 60000

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74408

African (AFR) AF: 0.0000241 AC: 1 AN: 41516

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.000280

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	MEF2C-related disorder (1)
-	-	1	Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.0
DANN	Benign	0.70
PhyloP100		0.18
PromoterAI		-0.0082	Neutral
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79455305; hg19: chr5-88027714;