rs6115181

Variant names:

• chr20-2613608-A-G
• rs6115181
• NM_080751.3:c.1872+286A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080751.3(TMC2):​c.1872+286A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 381,876 control chromosomes in the GnomAD database, including 11,899 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4344 hom., cov: 32)
  • Exomes 𝑓: 0.25 (7555 hom.)
• Consequence: TMC2 NM_080751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 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.1872+286A>G		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.1872+286A>G		intron	N/A	ENSP00000351732.1	Q8TDI7-1
	TMC2	ENST00000496948.2	TSL:2	n.*160A>G		non_coding_transcript_exon	Exon 4 of 6	ENSP00000495303.1	A0A2R8YFP4
	TMC2	ENST00000496948.2	TSL:2	n.*160A>G		3_prime_UTR	Exon 4 of 6	ENSP00000495303.1	A0A2R8YFP4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35884 AN: 151932 Hom.: 4345 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.250 AC: 57515 AN: 229826 Hom.: 7555 Cov.: 3 AF XY: 0.254 AC XY: 31775 AN XY: 125256

African (AFR) AF: 0.223 AC: 1452 AN: 6498

American (AMR) AF: 0.299 AC: 3486 AN: 11664

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 1534 AN: 5834

East Asian (EAS) AF: 0.311 AC: 3276 AN: 10524

South Asian (SAS) AF: 0.290 AC: 11988 AN: 41274

European-Finnish (FIN) AF: 0.242 AC: 2455 AN: 10152

Middle Eastern (MID) AF: 0.325 AC: 340 AN: 1046

European-Non Finnish (NFE) AF: 0.229 AC: 30047 AN: 131108

Other (OTH) AF: 0.250 AC: 2937 AN: 11726

GnomAD4 genome AF: 0.236 AC: 35905 AN: 152050 Hom.: 4344 Cov.: 32 AF XY: 0.237 AC XY: 17619 AN XY: 74312

African (AFR) AF: 0.213 AC: 8850 AN: 41472

American (AMR) AF: 0.251 AC: 3841 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1574 AN: 5164

South Asian (SAS) AF: 0.295 AC: 1419 AN: 4812

European-Finnish (FIN) AF: 0.249 AC: 2640 AN: 10582

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15806 AN: 67954

Other (OTH) AF: 0.266 AC: 562 AN: 2114

Alfa AF: 0.239 Hom.: 7704

Bravo AF: 0.240

Asia WGS AF: 0.299 AC: 1039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.38
PhyloP100		-0.47
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: rs6115181; hg19: chr20-2594254;