rs10485602

chr20-2613856-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080751.3(TMC2):c.1872+534T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 189,500 control chromosomes in the GnomAD database, including 2,190 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 (1712 hom., cov: 32)
  • Exomes 𝑓: 0.14 (478 hom.)
• Consequence: TMC2 NM_080751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC2	NM_080751.3	c.1872+534T>C		intron_variant		ENST00000358864.2
TMC2	XM_005260660.5	c.1947+534T>C		intron_variant
TMC2	XR_001754152.2	n.2615T>C		non_coding_transcript_exon_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC2	ENST00000358864.2	c.1872+534T>C		intron_variant		1	NM_080751.3	P1
TMC2	ENST00000644205.1	n.1959T>C		non_coding_transcript_exon_variant	13/15
TMC2	ENST00000496948.2	c.*408T>C		3_prime_UTR_variant, NMD_transcript_variant	4/6	2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21120 AN: 152118 Hom.: 1712 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.141 AC: 5243 AN: 37264 Hom.: 478 Cov.: 0 AF XY: 0.138 AC XY: 2730 AN XY: 19714

Gnomad4 AFR exome AF: 0.0651

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.00888

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.139 AC: 21126 AN: 152236 Hom.: 1712 Cov.: 32 AF XY: 0.136 AC XY: 10124 AN XY: 74420

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.161

Alfa AF: 0.149 Hom.: 384

Bravo AF: 0.137

Asia WGS AF: 0.0650 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	4.8
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10485602; hg19: chr20-2594502;