rs10485603

chr20-2614869-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.1873-1268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,018 control chromosomes in the GnomAD database, including 1,567 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 0.13 (1567 hom., cov: 32)
• Consequence: TMC2 NM_080751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

LOC105372505 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC2	NM_080751.3	c.1873-1268T>C		intron_variant		ENST00000358864.2
LOC105372505	XR_007067502.1	n.938-737A>G		intron_variant, non_coding_transcript_variant
TMC2	XM_005260660.5	c.1948-1268T>C		intron_variant
TMC2	XR_001754152.2	n.2779+849T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC2	ENST00000358864.2	c.1873-1268T>C		intron_variant		1	NM_080751.3	P1
TMC2	ENST00000496948.2	c.*572+849T>C		intron_variant, NMD_transcript_variant		2
TMC2	ENST00000644205.1	n.2123+849T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19190 AN: 151900 Hom.: 1570 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.148

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19180 AN: 152018 Hom.: 1567 Cov.: 32 AF XY: 0.124 AC XY: 9234 AN XY: 74360

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.145

Alfa AF: 0.169 Hom.: 2235

Bravo AF: 0.122

Asia WGS AF: 0.0620 AC: 215 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.097
Dann	Benign	0.58

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: rs10485603; hg19: chr20-2595515;