chrX-154030353-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The allele frequency of the c.*14G>A variant in MECP2 (NM_004992) is 0.34% in South Asian sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). In summary the c.*14G>A variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA222800/MONDO:0010726/016

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., 14 hem., cov: 23)

Exomes 𝑓: 0.00047 ( 2 hom. 195 hem. )

Consequence

MECP2
NM_001110792.2 3_prime_UTR

Scores

Clinical Significance

Benign reviewed by expert panel U:3B:6

Conservation

PhyloP100: 1.86

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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet, G2P
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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

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	Effect	Exon Rank	Protein	UniProt
MECP2	NM_001110792.2	MANE Select	c.*14G>A	3_prime_UTR	Exon 3 of 3	NP_001104262.1	A0A140VKC4
MECP2	NM_004992.4	MANE Plus Clinical	c.*14G>A	3_prime_UTR	Exon 4 of 4	NP_004983.1	D3YJ43
MECP2	NM_001316337.2		c.*14G>A	3_prime_UTR	Exon 5 of 5	NP_001303266.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MECP2	ENST00000453960.7	TSL:1 MANE Select	c.*14G>A	3_prime_UTR	Exon 3 of 3	ENSP00000395535.2	P51608-2
MECP2	ENST00000303391.11	TSL:1 MANE Plus Clinical	c.*14G>A	3_prime_UTR	Exon 4 of 4	ENSP00000301948.6	P51608-1
MECP2	ENST00000630151.3	TSL:5	c.*14G>A	3_prime_UTR	Exon 4 of 4	ENSP00000486089.2	P51608-1

Frequencies

GnomAD3 genomes

AF:

0.000350

AC:

AN:

111469

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000945

Gnomad ASJ

AF:

0.000380

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00155

Gnomad FIN

AF:

0.000330

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000321

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000741

AC:

136

AN:

183429

AF XY:

0.000751

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000729

Gnomad ASJ exome

AF:

0.000534

Gnomad EAS exome

AF:

0.0000721

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000476

Gnomad OTH exome

AF:

0.000883

GnomAD4 exome

AF:

0.000468

AC:

514

AN:

1098157

Hom.:

Cov.:

AF XY:

0.000536

AC XY:

195

AN XY:

363517

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26401

American (AMR)

AF:

0.000625

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.000413

AC:

AN:

19386

East Asian (EAS)

AF:

0.000132

AC:

AN:

30206

South Asian (SAS)

AF:

0.00299

AC:

162

AN:

54147

European-Finnish (FIN)

AF:

0.0000494

AC:

AN:

40493

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000338

AC:

285

AN:

842086

Other (OTH)

AF:

0.000607

AC:

AN:

46095

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000350

AC:

AN:

111522

Hom.:

Cov.:

AF XY:

0.000415

AC XY:

AN XY:

33714

show subpopulations

African (AFR)

AF:

0.000163

AC:

AN:

30698

American (AMR)

AF:

0.000944

AC:

AN:

10593

Ashkenazi Jewish (ASJ)

AF:

0.000380

AC:

AN:

2633

East Asian (EAS)

AF:

0.00

AC:

AN:

3556

South Asian (SAS)

AF:

0.00155

AC:

AN:

2573

European-Finnish (FIN)

AF:

0.000330

AC:

AN:

6068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.000321

AC:

AN:

52978

Other (OTH)

AF:

0.00

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000334

Hom.:

Bravo

AF:

0.000374

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Rett syndrome (3)

not provided (2)

MECP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.9

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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