chr11-22263072-G-T

Variant names:

• chr11-22263072-G-T
• rs76084798
• NM_213599.3:c.1898+29G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213599.3(ANO5):​c.1898+29G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00544 in 1,535,890 control chromosomes in the GnomAD database, including 362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (197 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (165 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.438
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-22263072-G-T is Benign according to our data. Variant chr11-22263072-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0956 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.1898+29G>T		intron	N/A	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.1895+29G>T		intron	N/A	NP_001136121.1
	ANO5	NM_001410963.1		c.1856+29G>T		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.1898+29G>T		intron	N/A	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.1856+29G>T		intron	N/A	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.1853+29G>T		intron	N/A	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4316 AN: 152026 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0279

GnomAD2 exomes AF: 0.00739 AC: 1841 AN: 249268 AF XY: 0.00541

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.00540

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000266

Gnomad OTH exome AF: 0.00412

GnomAD4 exome AF: 0.00291 AC: 4032 AN: 1383746 Hom.: 165 Cov.: 23 AF XY: 0.00249 AC XY: 1724 AN XY: 692962

African (AFR) AF: 0.0988 AC: 3143 AN: 31816

American (AMR) AF: 0.00628 AC: 280 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25690

East Asian (EAS) AF: 0.00 AC: 0 AN: 39138

South Asian (SAS) AF: 0.000319 AC: 27 AN: 84618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52478

Middle Eastern (MID) AF: 0.00535 AC: 30 AN: 5610

European-Non Finnish (NFE) AF: 0.000146 AC: 152 AN: 1042014

Other (OTH) AF: 0.00692 AC: 400 AN: 57818

GnomAD4 genome AF: 0.0284 AC: 4323 AN: 152144 Hom.: 197 Cov.: 32 AF XY: 0.0278 AC XY: 2070 AN XY: 74400

African (AFR) AF: 0.0981 AC: 4071 AN: 41494

American (AMR) AF: 0.0116 AC: 178 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67988

Other (OTH) AF: 0.0276 AC: 58 AN: 2104

Alfa AF: 0.00858 Hom.: 12

Bravo AF: 0.0325

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.53
PhyloP100		-0.44
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: rs76084798; hg19: chr11-22284618;