chr20-2613544-C-T

Variant names:

• chr20-2613544-C-T
• rs10485601
• NM_080751.3:c.1872+222C>T

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+222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 551,424 control chromosomes in the GnomAD database, including 7,061 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 0.14 (1650 hom., cov: 32)
  • Exomes 𝑓: 0.16 (5411 hom.)
• Consequence: TMC2 NM_080751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC2	NM_080751.3	MANE Select	c.1872+222C>T		intron	N/A	NP_542789.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC2	ENST00000358864.2	TSL:1 MANE Select	c.1872+222C>T		intron	N/A	ENSP00000351732.1
	TMC2	ENST00000496948.2	TSL:2	n.*96C>T		non_coding_transcript_exon	Exon 4 of 6	ENSP00000495303.1
	TMC2	ENST00000496948.2	TSL:2	n.*96C>T		3_prime_UTR	Exon 4 of 6	ENSP00000495303.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20604 AN: 152012 Hom.: 1652 Cov.: 32

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.157 AC: 62635 AN: 399294 Hom.: 5411 Cov.: 6 AF XY: 0.155 AC XY: 33286 AN XY: 214288

African (AFR) AF: 0.0669 AC: 752 AN: 11244

American (AMR) AF: 0.138 AC: 3129 AN: 22642

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 2461 AN: 11108

East Asian (EAS) AF: 0.0109 AC: 208 AN: 19142

South Asian (SAS) AF: 0.125 AC: 6107 AN: 48870

European-Finnish (FIN) AF: 0.156 AC: 2808 AN: 18046

Middle Eastern (MID) AF: 0.229 AC: 693 AN: 3030

European-Non Finnish (NFE) AF: 0.176 AC: 43055 AN: 244420

Other (OTH) AF: 0.165 AC: 3422 AN: 20792

GnomAD4 genome AF: 0.135 AC: 20599 AN: 152130 Hom.: 1650 Cov.: 32 AF XY: 0.133 AC XY: 9857 AN XY: 74348

African (AFR) AF: 0.0665 AC: 2761 AN: 41514

American (AMR) AF: 0.143 AC: 2191 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3470

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5184

South Asian (SAS) AF: 0.113 AC: 547 AN: 4820

European-Finnish (FIN) AF: 0.155 AC: 1638 AN: 10562

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12017 AN: 67994

Other (OTH) AF: 0.156 AC: 329 AN: 2106

Alfa AF: 0.161 Hom.: 1702

Bravo AF: 0.133

Asia WGS AF: 0.0640 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.4
DANN	Benign	0.73
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10485601; hg19: chr20-2594190;