rs398123566

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3BP6_Very_StrongBS2

The NM_001110792.2(MECP2):c.15_23delCGCCGCCGC(p.Ala6_Ala8del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000898 in 1,024,866 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★★). Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Likely benign. The gene MECP2 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000097 ( 0 hom. 26 hem. )

Consequence

MECP2
NM_001110792.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel U:2B:6

Conservation

PhyloP100: 4.00

Publications

3 publications found

Variant links:

Genes affected

MECP2 (HGNC:6990): (methyl-CpG binding protein 2) DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

MECP2 Gene-Disease associations (from GenCC):

chromosome Xq28 duplication syndrome
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
Rett syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
severe neonatal-onset encephalopathy with microcephaly
Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
syndromic X-linked intellectual disability Lubs type
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
atypical Rett syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability-psychosis-macroorchidism syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

MECP2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001110792.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for MECP2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001110792.2

BP6

Variant X-154097642-CGCGGCGGCG-C is Benign according to our data. Variant chrX-154097642-CGCGGCGGCG-C is described in ClinVar as Benign. ClinVar VariationId is 193163.Status of the report is reviewed_by_expert_panel, 3 stars.

BS2

High AC in GnomAdExome4 at 89 XL,Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001110792.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MECP2	NM_001110792.2	MANE Select	c.15_23delCGCCGCCGC	p.Ala6_Ala8del	disruptive_inframe_deletion	Exon 1 of 3	NP_001104262.1	A0A140VKC4
MECP2	NM_004992.4	MANE Plus Clinical	c.-146_-138delCGCCGCCGC		5_prime_UTR	Exon 1 of 4	NP_004983.1	D3YJ43
MECP2	NM_001316337.2		c.-593_-585delCGCCGCCGC		5_prime_UTR	Exon 1 of 5	NP_001303266.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MECP2	ENST00000453960.7	TSL:1 MANE Select	c.15_23delCGCCGCCGC	p.Ala6_Ala8del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000395535.2	P51608-2
MECP2	ENST00000303391.11	TSL:1 MANE Plus Clinical	c.-146_-138delCGCCGCCGC		5_prime_UTR	Exon 1 of 4	ENSP00000301948.6	P51608-1
MECP2	ENST00000631210.1	TSL:1	n.305+7130_305+7138delCGCCGCCGC		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000282

AC:

AN:

106553

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000393

Gnomad OTH

AF:

0.000695

GnomAD2 exomes

AF:

0.0000500

AC:

AN:

59976

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000969

AC:

AN:

918313

Hom.:

AF XY:

0.0000912

AC XY:

AN XY:

284941

show subpopulations

African (AFR)

AF:

0.0000504

AC:

AN:

19838

American (AMR)

AF:

0.0000584

AC:

AN:

17111

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13271

East Asian (EAS)

AF:

0.00

AC:

AN:

22385

South Asian (SAS)

AF:

0.0000944

AC:

AN:

31778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3234

European-Non Finnish (NFE)

AF:

0.000106

AC:

AN:

752170

Other (OTH)

AF:

0.000108

AC:

AN:

36892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000282

AC:

AN:

106553

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

30189

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29680

American (AMR)

AF:

0.00

AC:

AN:

10343

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2596

East Asian (EAS)

AF:

0.00

AC:

AN:

3256

South Asian (SAS)

AF:

0.00

AC:

AN:

2499

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5017

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.0000393

AC:

AN:

50882

Other (OTH)

AF:

0.000695

AC:

AN:

1438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Rett syndrome (2)

MECP2-related disorder (1)

Severe neonatal-onset encephalopathy with microcephaly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over