20-2562023-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080751.3(TMC2):c.554+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,610,544 control chromosomes in the GnomAD database, including 98,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8078 hom., cov: 34)
  • Exomes 𝑓: 0.35 (90654 hom.)
• Consequence: TMC2 NM_080751.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.965

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-2562023-C-T is Benign according to our data. Variant chr20-2562023-C-T is described in ClinVar as [Benign]. Clinvar id is 1246774.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC2	NM_080751.3	c.554+13C>T		intron_variant		ENST00000358864.2
TMC2	XM_005260660.5	c.629+13C>T		intron_variant
TMC2	XR_001754152.2	n.763+13C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC2	ENST00000358864.2	c.554+13C>T		intron_variant		1	NM_080751.3	P1
TMC2	ENST00000644205.1	n.713+13C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47667 AN: 152126 Hom.: 8078 Cov.: 34

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.353

GnomAD3 exomes AF: 0.346 AC: 85111 AN: 246262 Hom.: 15435 AF XY: 0.349 AC XY: 46600 AN XY: 133384

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.303

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.490

Gnomad SAS exome AF: 0.328

Gnomad FIN exome AF: 0.275

Gnomad NFE exome AF: 0.361

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.349 AC: 508805 AN: 1458300 Hom.: 90654 Cov.: 34 AF XY: 0.350 AC XY: 253530 AN XY: 725378

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.313 AC: 47680 AN: 152244 Hom.: 8078 Cov.: 34 AF XY: 0.313 AC XY: 23263 AN XY: 74426

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.354

Alfa AF: 0.352 Hom.: 1827

Bravo AF: 0.313

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.3
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs7270277; hg19: chr20-2542669; COSMIC: COSV62649511;