20-2562023-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080751.3(TMC2):​c.554+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,610,544 control chromosomes in the GnomAD database, including 98,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8078 hom., cov: 34)
Exomes 𝑓: 0.35 ( 90654 hom. )

Consequence

TMC2
NM_080751.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.965
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 20-2562023-C-T is Benign according to our data. Variant chr20-2562023-C-T is described in ClinVar as [Benign]. Clinvar id is 1246774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMC2NM_080751.3 linkuse as main transcriptc.554+13C>T intron_variant ENST00000358864.2
TMC2XM_005260660.5 linkuse as main transcriptc.629+13C>T intron_variant
TMC2XR_001754152.2 linkuse as main transcriptn.763+13C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMC2ENST00000358864.2 linkuse as main transcriptc.554+13C>T intron_variant 1 NM_080751.3 P1Q8TDI7-1
TMC2ENST00000644205.1 linkuse as main transcriptn.713+13C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.313
AC:
47667
AN:
152126
Hom.:
8078
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.195
Gnomad AMI
AF:
0.427
Gnomad AMR
AF:
0.361
Gnomad ASJ
AF:
0.503
Gnomad EAS
AF:
0.469
Gnomad SAS
AF:
0.322
Gnomad FIN
AF:
0.268
Gnomad MID
AF:
0.506
Gnomad NFE
AF:
0.356
Gnomad OTH
AF:
0.353
GnomAD3 exomes
AF:
0.346
AC:
85111
AN:
246262
Hom.:
15435
AF XY:
0.349
AC XY:
46600
AN XY:
133384
show subpopulations
Gnomad AFR exome
AF:
0.190
Gnomad AMR exome
AF:
0.303
Gnomad ASJ exome
AF:
0.487
Gnomad EAS exome
AF:
0.490
Gnomad SAS exome
AF:
0.328
Gnomad FIN exome
AF:
0.275
Gnomad NFE exome
AF:
0.361
Gnomad OTH exome
AF:
0.381
GnomAD4 exome
AF:
0.349
AC:
508805
AN:
1458300
Hom.:
90654
Cov.:
34
AF XY:
0.350
AC XY:
253530
AN XY:
725378
show subpopulations
Gnomad4 AFR exome
AF:
0.188
Gnomad4 AMR exome
AF:
0.309
Gnomad4 ASJ exome
AF:
0.488
Gnomad4 EAS exome
AF:
0.493
Gnomad4 SAS exome
AF:
0.330
Gnomad4 FIN exome
AF:
0.284
Gnomad4 NFE exome
AF:
0.350
Gnomad4 OTH exome
AF:
0.361
GnomAD4 genome
AF:
0.313
AC:
47680
AN:
152244
Hom.:
8078
Cov.:
34
AF XY:
0.313
AC XY:
23263
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.194
Gnomad4 AMR
AF:
0.361
Gnomad4 ASJ
AF:
0.503
Gnomad4 EAS
AF:
0.469
Gnomad4 SAS
AF:
0.323
Gnomad4 FIN
AF:
0.268
Gnomad4 NFE
AF:
0.356
Gnomad4 OTH
AF:
0.354
Alfa
AF:
0.352
Hom.:
1827
Bravo
AF:
0.313

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
4.3
DANN
Benign
0.76

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7270277; hg19: chr20-2542669; COSMIC: COSV62649511; API