GeneBe

rs35401252

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003289.4(TPM2):​c.773-8_773-3delCCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,343,400 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

TPM2
NM_003289.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

Publications

0 publications found
Variant links:
Genes affected
TPM2 (HGNC:12011): (tropomyosin 2) This gene encodes beta-tropomyosin, a member of the actin filament binding protein family, and mainly expressed in slow, type 1 muscle fibers. Mutations in this gene can alter the expression of other sarcomeric tropomyosin proteins, and cause cap disease, nemaline myopathy and distal arthrogryposis syndromes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]
TPM2 Gene-Disease associations (from GenCC):
  • TPM2-related myopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • arthrogryposis, distal, type 1A
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • congenital myopathy 23
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • congenital myopathy
    Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
  • cap myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • childhood-onset nemaline myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • congenital fiber-type disproportion myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • digitotalar dysmorphism
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Sheldon-hall syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • typical nemaline myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TPM2NM_003289.4 linkc.773-8_773-3delCCCCCC splice_region_variant, intron_variant Intron 8 of 8 ENST00000645482.3 NP_003280.2
TPM2NM_001301226.2 linkc.772+997_772+1002delCCCCCC intron_variant Intron 8 of 8 NP_001288155.1
TPM2NM_001301227.2 linkc.773-8_773-3delCCCCCC splice_region_variant, intron_variant Intron 8 of 8 NP_001288156.1
TPM2NM_213674.1 linkc.772+997_772+1002delCCCCCC intron_variant Intron 8 of 8 NP_998839.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TPM2ENST00000645482.3 linkc.773-8_773-3delCCCCCC splice_region_variant, intron_variant Intron 8 of 8 NM_003289.4 ENSP00000496494.2

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000149
AC:
2
AN:
1343400
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
664396
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
30778
American (AMR)
AF:
0.00
AC:
0
AN:
35502
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24482
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35382
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78308
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48500
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5554
European-Non Finnish (NFE)
AF:
0.00000194
AC:
2
AN:
1028994
Other (OTH)
AF:
0.00
AC:
0
AN:
55900
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.2

Splicing

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

Publications

Other links and lift over

dbSNP: rs35401252; hg19: chr9-35683240; API