chr11-22262094-G-A

Variant names:

• chr11-22262094-G-A
• rs72982041
• NM_213599.3:c.1631-35G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_213599.3(ANO5):​c.1631-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,606,742 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (12 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.161
• Publications: 0 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):

• 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)

ENSG00000255372 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-22262094-G-A is Benign according to our data. Variant chr11-22262094-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 263312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

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.1631-35G>A		intron	N/A	NP_998764.1
	ANO5	NM_001142649.2		c.1628-35G>A		intron	N/A	NP_001136121.1
	ANO5	NM_001410963.1		c.1589-35G>A		intron	N/A	NP_001397892.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	ENST00000324559.9	TSL:1 MANE Select	c.1631-35G>A		intron	N/A	ENSP00000315371.9
	ANO5	ENST00000682341.1		c.1589-35G>A		intron	N/A	ENSP00000508251.1
	ANO5	ENST00000684663.1		c.1586-35G>A		intron	N/A	ENSP00000508009.1

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 491 AN: 152134 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00519

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00465

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00354 AC: 883 AN: 249610 AF XY: 0.00348

Gnomad AFR exome AF: 0.000740

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00573

Gnomad NFE exome AF: 0.00575

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00358 AC: 5211 AN: 1454490 Hom.: 12 Cov.: 29 AF XY: 0.00357 AC XY: 2586 AN XY: 724010

African (AFR) AF: 0.000661 AC: 22 AN: 33274

American (AMR) AF: 0.00215 AC: 96 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 54 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.000581 AC: 50 AN: 86048

European-Finnish (FIN) AF: 0.00655 AC: 345 AN: 52676

Middle Eastern (MID) AF: 0.00185 AC: 9 AN: 4872

European-Non Finnish (NFE) AF: 0.00401 AC: 4440 AN: 1107216

Other (OTH) AF: 0.00325 AC: 195 AN: 60076

GnomAD4 genome AF: 0.00322 AC: 490 AN: 152252 Hom.: 3 Cov.: 32 AF XY: 0.00306 AC XY: 228 AN XY: 74448

African (AFR) AF: 0.000746 AC: 31 AN: 41552

American (AMR) AF: 0.00222 AC: 34 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00519 AC: 55 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00465 AC: 316 AN: 67996

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00373 Hom.: 0

Bravo AF: 0.00326

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism

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: rs72982041; hg19: chr11-22283640;