1-156479595-C-G

Position:

• chr1-156479595-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005920.4(MEF2D):​c.598G>C​(p.Ala200Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEF2D NM_005920.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09

Genes affected

MEF2D (HGNC:6997): (myocyte enhancer factor 2D) This gene is a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors. Members of this family are involved in control of muscle and neuronal cell differentiation and development, and are regulated by class II histone deacetylases. Fusions of the encoded protein with Deleted in Azoospermia-Associated Protein 1 (DAZAP1) due to a translocation have been found in an acute lymphoblastic leukemia cell line, suggesting a role in leukemogenesis. The encoded protein may also be involved in Parkinson disease and myotonic dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

MEF2D (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22877127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2D	NM_005920.4	c.598G>C	p.Ala200Pro	missense_variant	5/12	ENST00000348159.9	NP_005911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2D	ENST00000348159.9	c.598G>C	p.Ala200Pro	missense_variant	5/12	1	NM_005920.4	ENSP00000271555.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

MEF2D-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2023

The MEF2D c.598G>C variant is predicted to result in the amino acid substitution p.Ala200Pro. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.078	.;T;.
Eigen	Benign	-0.022
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.49	.;N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	2.1	.;N;N
REVEL	Benign	0.26
Sift	Benign	1.0	.;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0070, 0.0060	.;B;B
Vest4		0.31
MutPred		0.085		.;Gain of glycosylation at A200 (P = 0.0263);Gain of glycosylation at A200 (P = 0.0263);
MVP		0.65
MPC		1.2
ClinPred		0.94	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156449387;