GeneBe

11-22274548-CTTTTT-CTTTTTTTTTTTT

Variant names:

Variant summary

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

The NM_213599.3(ANO5):​c.2236-16_2236-10dupTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 1,119,966 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: 27)
Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

ANO5
NM_213599.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.693

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)

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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
ANO5NM_213599.3 linkc.2236-16_2236-10dupTTTTTTT intron_variant Intron 19 of 21 ENST00000324559.9 NP_998764.1 Q75V66

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANO5ENST00000324559.9 linkc.2236-21_2236-20insTTTTTTT intron_variant Intron 19 of 21 1 NM_213599.3 ENSP00000315371.9 Q75V66

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
AF:
0.00000179
AC:
2
AN:
1119966
Hom.:
0
Cov.:
0
AF XY:
0.00000181
AC XY:
1
AN XY:
553366
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
25834
American (AMR)
AF:
0.00
AC:
0
AN:
27506
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18298
East Asian (EAS)
AF:
0.00
AC:
0
AN:
28574
South Asian (SAS)
AF:
0.00
AC:
0
AN:
61924
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40450
Middle Eastern (MID)
AF:
0.000215
AC:
1
AN:
4644
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
866492
Other (OTH)
AF:
0.0000216
AC:
1
AN:
46244
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.69

Splicing

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

Publications

Other links and lift over

dbSNP: rs72105710; hg19: chr11-22296094; API