11-22274563-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_213599.3(ANO5):c.2236-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,389,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANO5 NM_213599.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002067
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0640

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-22274563-C-T is Benign according to our data. Variant chr11-22274563-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 468840.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-22274563-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO5	NM_213599.3	c.2236-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000324559.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO5	ENST00000324559.9	c.2236-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_213599.3	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 26 AN: 147160 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00138

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000135

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000465 AC: 646 AN: 1389038 Hom.: 0 Cov.: 33 AF XY: 0.000432 AC XY: 296 AN XY: 685154

Gnomad4 AFR exome AF: 0.00242

Gnomad4 AMR exome AF: 0.00550

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.000395

Gnomad4 SAS exome AF: 0.000444

Gnomad4 FIN exome AF: 0.000520

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.000683

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000177 AC: 26 AN: 147160 Hom.: 0 Cov.: 32 AF XY: 0.000210 AC XY: 15 AN XY: 71454

Gnomad4 AFR AF: 0.000100

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00138

Gnomad4 NFE AF: 0.000135

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0238 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 08, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.2
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.010
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

LitVar

Other links and lift over

dbSNP: rs755410266; hg19: chr11-22296109;