dbSNP rs6115181: TMC2:c.1872+286A>G (chr20-2613608-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.472

Publications

8 publications found

Variant links:

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]

TMC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TMC2	NM_080751.3 link	c.1872+286A>G	intron_variant	Intron 14 of 19	ENST00000358864.2	NP_542789.2	Q8TDI7-1
TMC2	XR_001754152.2 link	n.2367A>G	non_coding_transcript_exon_variant	Exon 12 of 13
TMC2	XM_005260660.5 link	c.1947+286A>G	intron_variant	Intron 12 of 17		XP_005260717.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMC2	ENST00000358864.2 link	c.1872+286A>G	intron_variant	Intron 14 of 19	1	NM_080751.3	ENSP00000351732.1	Q8TDI7-1
TMC2	ENST00000496948.2 link	n.*160A>G	non_coding_transcript_exon_variant	Exon 4 of 6	2		ENSP00000495303.1	A0A2R8YFP4
TMC2	ENST00000496948.2 link	n.*160A>G	3_prime_UTR_variant	Exon 4 of 6	2		ENSP00000495303.1	A0A2R8YFP4
TMC2	ENST00000644205.1 link	n.1936-225A>G	intron_variant	Intron 12 of 14

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35884

AN:

151932

Hom.:

4345

Cov.:

show subpopulations

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.:

AF XY:

0.254

AC XY:

31775

AN XY:

125256

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2016

4033

6049

8066

10082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

258

516

774

1032

1290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.236

AC:

35905

AN:

152050

Hom.:

4344

Cov.:

AF XY:

0.237

AC XY:

17619

AN XY:

74312

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.233

AC:

15806

AN:

67954

Other (OTH)

AF:

0.266

AC:

562

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1387

2775

4162

5550

6937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.5

(source)

DANN

Benign

0.38

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over