20-2572171-C-T

Variant summary

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

The NM_080751.3(TMC2):c.555-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00084 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMC2 NM_080751.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004928
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.894

Genes affected

TMC2 (HGNC:16527): (transmembrane channel like 2) This gene encodes a transmembrane protein that is necesssary for mechanotransduction in cochlear hair cells of the inner ear. Mutations in this gene may underlie hereditary disorders of balance and hearing. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-2572171-C-T is Benign according to our data. Variant chr20-2572171-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 769064.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC2	NM_080751.3	c.555-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000358864.2
TMC2	XM_005260660.5	c.630-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TMC2	XR_001754152.2	n.764-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC2	ENST00000358864.2	c.555-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_080751.3	P1
TMC2	ENST00000644205.1	n.714-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 68 AN: 116952 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000756

Gnomad ASJ AF: 0.000335

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00300

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000328

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000844 AC: 1145 AN: 1356554 Hom.: 1 Cov.: 32 AF XY: 0.000855 AC XY: 577 AN XY: 675146

Gnomad4 AFR exome AF: 0.00380

Gnomad4 AMR exome AF: 0.00435

Gnomad4 ASJ exome AF: 0.00196

Gnomad4 EAS exome AF: 0.000242

Gnomad4 SAS exome AF: 0.00204

Gnomad4 FIN exome AF: 0.00540

Gnomad4 NFE exome AF: 0.000355

Gnomad4 OTH exome AF: 0.000789

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000581 AC: 68 AN: 117000 Hom.: 0 Cov.: 29 AF XY: 0.000632 AC XY: 36 AN XY: 57002

Gnomad4 AFR AF: 0.00102

Gnomad4 AMR AF: 0.0000755

Gnomad4 ASJ AF: 0.000335

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00300

Gnomad4 NFE AF: 0.000328

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00319 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.2
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
SpliceAI score (max)		0.060		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: rs757672864; hg19: chr20-2552817;