2-71574167-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130987.2(DYSF):​c.3229-31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00957 in 1,609,936 control chromosomes in the GnomAD database, including 1,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 586 hom., cov: 33)
Exomes 𝑓: 0.0055 ( 539 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.34

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: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 2-71574167-G-A is Benign according to our data. Variant chr2-71574167-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYSFNM_001130987.2 linkc.3229-31G>A intron_variant Intron 29 of 55 ENST00000410020.8 NP_001124459.1 O75923-13
DYSFNM_003494.4 linkc.3175-31G>A intron_variant Intron 29 of 54 ENST00000258104.8 NP_003485.1 O75923-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYSFENST00000410020.8 linkc.3229-31G>A intron_variant Intron 29 of 55 1 NM_001130987.2 ENSP00000386881.3 O75923-13
DYSFENST00000258104.8 linkc.3175-31G>A intron_variant Intron 29 of 54 1 NM_003494.4 ENSP00000258104.3 O75923-1

Frequencies

GnomAD3 genomes
AF:
0.0488
AC:
7422
AN:
152174
Hom.:
587
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.165
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0271
Gnomad ASJ
AF:
0.0127
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.000720
Gnomad OTH
AF:
0.0402
GnomAD2 exomes
AF:
0.0135
AC:
3340
AN:
246806
AF XY:
0.0102
show subpopulations
Gnomad AFR exome
AF:
0.172
Gnomad AMR exome
AF:
0.00944
Gnomad ASJ exome
AF:
0.0182
Gnomad EAS exome
AF:
0.0000545
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000749
Gnomad OTH exome
AF:
0.00890
GnomAD4 exome
AF:
0.00547
AC:
7967
AN:
1457644
Hom.:
539
Cov.:
32
AF XY:
0.00473
AC XY:
3430
AN XY:
724598
show subpopulations
African (AFR)
AF:
0.172
AC:
5746
AN:
33430
American (AMR)
AF:
0.0109
AC:
489
AN:
44670
Ashkenazi Jewish (ASJ)
AF:
0.0178
AC:
466
AN:
26114
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39634
South Asian (SAS)
AF:
0.000360
AC:
31
AN:
86212
European-Finnish (FIN)
AF:
0.0000193
AC:
1
AN:
51888
Middle Eastern (MID)
AF:
0.0102
AC:
58
AN:
5676
European-Non Finnish (NFE)
AF:
0.000381
AC:
423
AN:
1109786
Other (OTH)
AF:
0.0125
AC:
752
AN:
60234
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
406
812
1217
1623
2029
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
186
372
558
744
930
<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:
0.0488
AC:
7436
AN:
152292
Hom.:
586
Cov.:
33
AF XY:
0.0468
AC XY:
3483
AN XY:
74476
show subpopulations
African (AFR)
AF:
0.165
AC:
6838
AN:
41542
American (AMR)
AF:
0.0271
AC:
415
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
0.0127
AC:
44
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.000622
AC:
3
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.0102
AC:
3
AN:
294
European-Non Finnish (NFE)
AF:
0.000720
AC:
49
AN:
68032
Other (OTH)
AF:
0.0398
AC:
84
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
320
640
960
1280
1600
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
76
152
228
304
380
<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:
0.0259
Hom.:
44
Bravo
AF:
0.0564
Asia WGS
AF:
0.0120
AC:
41
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jun 28, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.12
DANN
Benign
0.76
PhyloP100
-2.3
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs72902605; hg19: chr2-71801297; API