Genetic Variant NM_080751.3:c.1872+534T>C (chr20-2613856-T-C) – 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+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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.408

Publications

2 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:

LOC105372505 (HGNC:):

LOC105372505 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_080751.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC2	NM_080751.3	MANE Select	c.1872+534T>C		intron	N/A	NP_542789.2	Q8TDI7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMC2	ENST00000358864.2	TSL:1 MANE Select	c.1872+534T>C	intron	N/A	ENSP00000351732.1	Q8TDI7-1
TMC2	ENST00000496948.2	TSL:2	n.*408T>C	non_coding_transcript_exon	Exon 4 of 6	ENSP00000495303.1	A0A2R8YFP4
TMC2	ENST00000644205.1		n.1959T>C	non_coding_transcript_exon	Exon 13 of 15

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21120

AN:

152118

Hom.:

1712

Cov.:

show subpopulations

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.:

AF XY:

0.138

AC XY:

2730

AN XY:

19714

show subpopulations

African (AFR)

AF:

0.0651

AC:

AN:

830

American (AMR)

AF:

0.150

AC:

479

AN:

3204

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

153

AN:

774

East Asian (EAS)

AF:

0.00888

AC:

AN:

1914

South Asian (SAS)

AF:

0.116

AC:

548

AN:

4738

European-Finnish (FIN)

AF:

0.139

AC:

179

AN:

1284

Middle Eastern (MID)

AF:

0.228

AC:

AN:

114

European-Non Finnish (NFE)

AF:

0.156

AC:

3519

AN:

22498

Other (OTH)

AF:

0.140

AC:

268

AN:

1908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

218

437

655

874

1092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.139

AC:

21126

AN:

152236

Hom.:

1712

Cov.:

AF XY:

0.136

AC XY:

10124

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0769

AC:

3196

AN:

41554

American (AMR)

AF:

0.145

AC:

2209

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

789

AN:

3472

East Asian (EAS)

AF:

0.0106

AC:

AN:

5174

South Asian (SAS)

AF:

0.114

AC:

549

AN:

4828

European-Finnish (FIN)

AF:

0.156

AC:

1650

AN:

10600

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12062

AN:

68010

Other (OTH)

AF:

0.161

AC:

340

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

938

1876

2813

3751

4689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.148

Hom.:

387

Bravo

AF:

0.137

Asia WGS

AF:

0.0650

AC:

228

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

4.8

(source)

DANN

Benign

0.75

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over