chr11-22279537-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting

The NM_213599.3(ANO5):​c.2521-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,603,838 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 2 hom. )

Consequence

ANO5
NM_213599.3 splice_region, intron

Scores

2
Splicing: ADA: 0.00002760
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0980

Publications

0 publications found
Variant links:
Genes affected
ANO5 (HGNC:27337): (anoctamin 5) This gene encodes a member of the anoctamin family of transmembrane proteins. The encoded protein is likely a calcium activated chloride channel. Mutations in this gene have been associated with gnathodiaphyseal dysplasia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]
ANO5 Gene-Disease associations (from GenCC):
  • autosomal recessive limb-girdle muscular dystrophy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • gnathodiaphyseal dysplasia
    Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
  • autosomal recessive limb-girdle muscular dystrophy type 2L
    Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
  • Miyoshi muscular dystrophy 3
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 11-22279537-C-T is Benign according to our data. Variant chr11-22279537-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 282397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 AR,AD geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANO5NM_213599.3 linkc.2521-7C>T splice_region_variant, intron_variant Intron 21 of 21 ENST00000324559.9 NP_998764.1 Q75V66

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANO5ENST00000324559.9 linkc.2521-7C>T splice_region_variant, intron_variant Intron 21 of 21 1 NM_213599.3 ENSP00000315371.9 Q75V66

Frequencies

GnomAD3 genomes
AF:
0.00103
AC:
157
AN:
151852
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00372
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000321
AC:
80
AN:
249164
AF XY:
0.000230
show subpopulations
Gnomad AFR exome
AF:
0.00457
Gnomad AMR exome
AF:
0.0000582
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:
0.000328
GnomAD4 exome
AF:
0.000121
AC:
175
AN:
1451868
Hom.:
2
Cov.:
31
AF XY:
0.000111
AC XY:
80
AN XY:
722822
show subpopulations
African (AFR)
AF:
0.00418
AC:
139
AN:
33230
American (AMR)
AF:
0.0000898
AC:
4
AN:
44544
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26046
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39614
South Asian (SAS)
AF:
0.0000349
AC:
3
AN:
85994
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53320
Middle Eastern (MID)
AF:
0.000596
AC:
3
AN:
5030
European-Non Finnish (NFE)
AF:
0.00000272
AC:
3
AN:
1104076
Other (OTH)
AF:
0.000383
AC:
23
AN:
60014
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
8
16
23
31
39
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00103
AC:
156
AN:
151970
Hom.:
0
Cov.:
32
AF XY:
0.000875
AC XY:
65
AN XY:
74302
show subpopulations
African (AFR)
AF:
0.00369
AC:
153
AN:
41518
American (AMR)
AF:
0.000131
AC:
2
AN:
15246
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67818
Other (OTH)
AF:
0.00
AC:
0
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
11
22
32
43
54
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.000540
Hom.:
0
Bravo
AF:
0.00128
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Miyoshi muscular dystrophy 3 Benign:1
Dec 05, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
Oct 19, 2016
Eurofins Ntd Llc (ga)
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Apr 29, 2019
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Gnathodiaphyseal dysplasia Benign:1
Dec 05, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L Benign:1
Jan 25, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2L Benign:1
Dec 05, 2021
Genome-Nilou Lab
Significance: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
-0.81
CADD
Benign
6.0
DANN
Benign
0.64
PhyloP100
-0.098
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000028
dbscSNV1_RF
Benign
0.0020
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: rs201438159; hg19: chr11-22301083; API