chr20-2562023-C-T

Variant names:

• chr20-2562023-C-T
• rs7270277
• NM_080751.3:c.554+13C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.965
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1246774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080751.3. 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
	TMC2	NM_080751.3	MANE Select	c.554+13C>T		intron	N/A	NP_542789.2	Q8TDI7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC2	ENST00000358864.2	TSL:1 MANE Select	c.554+13C>T		intron	N/A	ENSP00000351732.1	Q8TDI7-1
	TMC2	ENST00000644205.1		n.713+13C>T		intron	N/A

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

GnomAD2 exomes AF: 0.346 AC: 85111 AN: 246262 AF XY: 0.349

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 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

African (AFR) AF: 0.188 AC: 6272 AN: 33308

American (AMR) AF: 0.309 AC: 13673 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 12660 AN: 25926

East Asian (EAS) AF: 0.493 AC: 19538 AN: 39658

South Asian (SAS) AF: 0.330 AC: 28324 AN: 85790

European-Finnish (FIN) AF: 0.284 AC: 15103 AN: 53222

Middle Eastern (MID) AF: 0.474 AC: 2676 AN: 5650

European-Non Finnish (NFE) AF: 0.350 AC: 388815 AN: 1110248

Other (OTH) AF: 0.361 AC: 21744 AN: 60214

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

African (AFR) AF: 0.194 AC: 8073 AN: 41566

American (AMR) AF: 0.361 AC: 5522 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3472

East Asian (EAS) AF: 0.469 AC: 2424 AN: 5168

South Asian (SAS) AF: 0.323 AC: 1563 AN: 4834

European-Finnish (FIN) AF: 0.268 AC: 2839 AN: 10598

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24233 AN: 67980

Other (OTH) AF: 0.354 AC: 747 AN: 2112

Alfa AF: 0.352 Hom.: 1827

Bravo AF: 0.313

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.76
PhyloP100		-0.96
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: rs7270277; hg19: chr20-2542669; COSMIC: COSV62649511;