rs6049839

chr20-2537919-G-T

Variant summary

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

The NM_080751.3(TMC2):c.82+603G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,962 control chromosomes in the GnomAD database, including 11,083 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 0.37 (11083 hom., cov: 31)
• Consequence: TMC2 NM_080751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

LOC105372504 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC2	NM_080751.3	c.82+603G>T		intron_variant		ENST00000358864.2
LOC105372504	XR_937204.3	n.401-3309C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC2	ENST00000358864.2	c.82+603G>T		intron_variant		1	NM_080751.3	P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56500 AN: 151844 Hom.: 11082 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.372 AC: 56511 AN: 151962 Hom.: 11083 Cov.: 31 AF XY: 0.376 AC XY: 27937 AN XY: 74296

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.383

Alfa AF: 0.416 Hom.: 31018

Bravo AF: 0.369

Asia WGS AF: 0.353 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.25
Dann	Benign	0.42

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: rs6049839; hg19: chr20-2518565;