rs535087290

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003494.4(DYSF):​c.-327G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000401 in 249,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

DYSF
NM_003494.4 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

Publications

0 publications found
Variant links:
Genes affected
DYSF (HGNC:3097): (dysferlin) The protein encoded by this gene belongs to the ferlin family and is a skeletal muscle protein found associated with the sarcolemma. It is involved in muscle contraction and contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. In addition, the protein encoded by this gene binds caveolin-3, a skeletal muscle membrane protein which is important in the formation of caveolae. Specific mutations in this gene have been shown to cause autosomal recessive limb girdle muscular dystrophy type 2B (LGMD2B) as well as Miyoshi myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2008]
DYSF Gene-Disease associations (from GenCC):
  • autosomal recessive limb-girdle muscular dystrophy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • neuromuscular disease caused by qualitative or quantitative defects of dysferlin
    Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
  • autosomal recessive limb-girdle muscular dystrophy type 2B
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
  • distal myopathy with anterior tibial onset
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • congenital myopathy, Paradas type
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Miyoshi myopathy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYSFNM_003494.4 linkc.-327G>C 5_prime_UTR_variant Exon 1 of 55 ENST00000258104.8 NP_003485.1 O75923-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYSFENST00000258104.8 linkc.-327G>C 5_prime_UTR_variant Exon 1 of 55 1 NM_003494.4 ENSP00000258104.3 O75923-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000401
AC:
1
AN:
249544
Hom.:
0
Cov.:
0
AF XY:
0.00000750
AC XY:
1
AN XY:
133370
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
7264
American (AMR)
AF:
0.00
AC:
0
AN:
12432
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
6924
East Asian (EAS)
AF:
0.0000756
AC:
1
AN:
13220
South Asian (SAS)
AF:
0.00
AC:
0
AN:
40946
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
11798
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
976
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
142638
Other (OTH)
AF:
0.00
AC:
0
AN:
13346
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
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.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
19
DANN
Benign
0.82
PhyloP100
1.8
PromoterAI
0.079
Neutral

Splicing

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

Publications

Other links and lift over

dbSNP: rs535087290; hg19: chr2-71680802; API