NM_213599.3:c.2236-10delT

Variant names:

• chr11-22274548-CT-C
• rs72105710
• NM_213599.3:c.2236-10delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_213599.3(ANO5):​c.2236-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,076,456 control chromosomes in the GnomAD database, including 2,188 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (227 hom., cov: 27)
  • Exomes 𝑓: 0.12 (1961 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.693
• Publications: 3 publications found

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)

ACMG classification

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

• BP6: Variant 11-22274548-CT-C is Benign according to our data. Variant chr11-22274548-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1174994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0649 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	NM_213599.3	MANE Select	c.2236-10delT		intron	N/A	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.2233-10delT		intron	N/A	NP_001136121.1
	ANO5	NM_001410963.1		c.2194-10delT		intron	N/A	NP_001397892.1	A0A804HL91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	ENST00000324559.9	TSL:1 MANE Select	c.2236-20delT		intron	N/A	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.2194-20delT		intron	N/A	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.2191-20delT		intron	N/A	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7563 AN: 146856 Hom.: 227 Cov.: 27

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.0324

Gnomad EAS AF: 0.000395

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0387

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0415

GnomAD2 exomes AF: 0.145 AC: 16715 AN: 115060 AF XY: 0.148

Gnomad AFR exome AF: 0.0717

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.0889

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.124 AC: 115698 AN: 929528 Hom.: 1961 Cov.: 0 AF XY: 0.124 AC XY: 57040 AN XY: 459084

African (AFR) AF: 0.0636 AC: 1404 AN: 22074

American (AMR) AF: 0.0873 AC: 1972 AN: 22580

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 1461 AN: 14414

East Asian (EAS) AF: 0.0656 AC: 1280 AN: 19516

South Asian (SAS) AF: 0.103 AC: 5414 AN: 52572

European-Finnish (FIN) AF: 0.169 AC: 5909 AN: 34920

Middle Eastern (MID) AF: 0.0743 AC: 304 AN: 4090

European-Non Finnish (NFE) AF: 0.129 AC: 93396 AN: 721770

Other (OTH) AF: 0.121 AC: 4558 AN: 37592

GnomAD4 genome AF: 0.0515 AC: 7561 AN: 146928 Hom.: 227 Cov.: 27 AF XY: 0.0515 AC XY: 3684 AN XY: 71574

African (AFR) AF: 0.0298 AC: 1205 AN: 40376

American (AMR) AF: 0.0310 AC: 454 AN: 14636

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 109 AN: 3364

East Asian (EAS) AF: 0.000396 AC: 2 AN: 5048

South Asian (SAS) AF: 0.0227 AC: 105 AN: 4630

European-Finnish (FIN) AF: 0.106 AC: 1009 AN: 9482

Middle Eastern (MID) AF: 0.0385 AC: 11 AN: 286

European-Non Finnish (NFE) AF: 0.0666 AC: 4407 AN: 66194

Other (OTH) AF: 0.0413 AC: 83 AN: 2012

Alfa AF: 0.0439 Hom.: 12

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2L (1)
-	-	1	Gnathodiaphyseal dysplasia (1)
-	-	1	Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L (1)
-	-	1	Miyoshi muscular dystrophy 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69
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

Other links and lift over

dbSNP: rs72105710; hg19: chr11-22296094; COSMIC: COSV61083748;