11-22227286-CTT-CT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_213599.3(ANO5):c.364-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 1,597,934 control chromosomes in the GnomAD database, including 9,229 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★★). The gene ANO5 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.14 ( 4186 hom., cov: 30)

Exomes 𝑓: 0.027 ( 5043 hom. )

Consequence

ANO5
NM_213599.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel B:13

Conservation

PhyloP100: 0.00100

Publications

3 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):

gnathodiaphyseal dysplasia
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet
autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2L
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
Miyoshi muscular dystrophy 3
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ANO5 links:

Genome browser will be placed here

ACMG classification

Specifications for ANO5 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 11-22227286-CT-C is Benign according to our data. Variant chr11-22227286-CT-C is described in ClinVar as Benign. ClinVar VariationId is 96684.Status of the report is reviewed_by_expert_panel, 3 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213599.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANO5	NM_213599.3	MANE Select	c.364-8delT	splice_region intron	N/A	NP_998764.1	Q75V66
ANO5	NM_001142649.2		c.361-8delT	splice_region intron	N/A	NP_001136121.1
ANO5	NM_001410963.1		c.322-8delT	splice_region intron	N/A	NP_001397892.1	A0A804HL91

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANO5	ENST00000324559.9	TSL:1 MANE Select	c.364-15delT	intron	N/A	ENSP00000315371.9	Q75V66
ANO5	ENST00000682341.1		c.322-15delT	intron	N/A	ENSP00000508251.1	A0A804HL91
ANO5	ENST00000684663.1		c.319-15delT	intron	N/A	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20894

AN:

150926

Hom.:

4170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0504

Gnomad ASJ

AF:

0.00982

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.0727

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.00492

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.0633

AC:

15241

AN:

240806

AF XY:

0.0551

show subpopulations

Gnomad AFR exome

AF:

0.455

Gnomad AMR exome

AF:

0.0321

Gnomad ASJ exome

AF:

0.00881

Gnomad EAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.0136

Gnomad NFE exome

AF:

0.00537

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0266

AC:

38520

AN:

1446888

Hom.:

5043

Cov.:

AF XY:

0.0259

AC XY:

18658

AN XY:

720078

show subpopulations

African (AFR)

AF:

0.458

AC:

15264

AN:

33294

American (AMR)

AF:

0.0319

AC:

1414

AN:

44278

Ashkenazi Jewish (ASJ)

AF:

0.00887

AC:

229

AN:

25828

East Asian (EAS)

AF:

0.204

AC:

8036

AN:

39374

South Asian (SAS)

AF:

0.0585

AC:

5006

AN:

85640

European-Finnish (FIN)

AF:

0.0148

AC:

784

AN:

52966

Middle Eastern (MID)

AF:

0.0243

AC:

135

AN:

5562

European-Non Finnish (NFE)

AF:

0.00408

AC:

4486

AN:

1100212

Other (OTH)

AF:

0.0530

AC:

3166

AN:

59734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1660

3319

4979

6638

8298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.139

AC:

20955

AN:

151046

Hom.:

4186

Cov.:

AF XY:

0.136

AC XY:

10052

AN XY:

73750

show subpopulations

African (AFR)

AF:

0.438

AC:

18023

AN:

41188

American (AMR)

AF:

0.0503

AC:

762

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.00982

AC:

AN:

3464

East Asian (EAS)

AF:

0.213

AC:

1090

AN:

5120

South Asian (SAS)

AF:

0.0730

AC:

348

AN:

4770

European-Finnish (FIN)

AF:

0.0127

AC:

132

AN:

10374

Middle Eastern (MID)

AF:

0.0377

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00493

AC:

334

AN:

67688

Other (OTH)

AF:

0.106

AC:

221

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

627

1255

1882

2510

3137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

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

Alfa

AF:

0.00976

Hom.:

Asia WGS

AF:

0.165

AC:

574

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Autosomal recessive limb-girdle muscular dystrophy (1)

Autosomal recessive limb-girdle muscular dystrophy type 2L (1)

Gnathodiaphyseal dysplasia (1)

Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L (1)

Limb-girdle muscular dystrophy, recessive (1)

Miyoshi muscular dystrophy 3 (1)

Miyoshi myopathy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0010

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over