chr20-2592170-T-G

Position:

• chr20-2592170-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080751.3(TMC2):​c.835-140T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 533,816 control chromosomes in the GnomAD database, including 118,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28455 hom., cov: 32)
  • Exomes 𝑓: 0.68 (90008 hom.)
• Consequence: TMC2 NM_080751.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.58

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-2592170-T-G is Benign according to our data. Variant chr20-2592170-T-G is described in ClinVar as [Benign]. Clinvar id is 1260478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC2	NM_080751.3	c.835-140T>G		intron_variant		ENST00000358864.2
TMC2	XM_005260660.5	c.910-140T>G		intron_variant
TMC2	XR_001754152.2	n.1044-140T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC2	ENST00000358864.2	c.835-140T>G		intron_variant		1	NM_080751.3	P1
TMC2	ENST00000644205.1	n.994-140T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90778 AN: 151968 Hom.: 28458 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.681 AC: 260013 AN: 381730 Hom.: 90008 AF XY: 0.684 AC XY: 136102 AN XY: 199112

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.614

Gnomad4 EAS exome AF: 0.512

Gnomad4 SAS exome AF: 0.751

Gnomad4 FIN exome AF: 0.760

Gnomad4 NFE exome AF: 0.697

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.597 AC: 90790 AN: 152086 Hom.: 28455 Cov.: 32 AF XY: 0.601 AC XY: 44679 AN XY: 74350

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.597

Alfa AF: 0.634 Hom.: 3909

Bravo AF: 0.579

Asia WGS AF: 0.626 AC: 2177 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.4
DANN	Benign	0.43

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: rs6050433; hg19: chr20-2572816;