9-35682258-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000378292.9(TPM2):c.773-95C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,331,142 control chromosomes in the GnomAD database, including 36,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3381 hom., cov: 32)
  • Exomes 𝑓: 0.23 (33127 hom.)
• Consequence: TPM2 ENST00000378292.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.366

Genes affected

TPM2 (HGNC:12011): (tropomyosin 2) This gene encodes beta-tropomyosin, a member of the actin filament binding protein family, and mainly expressed in slow, type 1 muscle fibers. Mutations in this gene can alter the expression of other sarcomeric tropomyosin proteins, and cause cap disease, nemaline myopathy and distal arthrogryposis syndromes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-35682258-G-C is Benign according to our data. Variant chr9-35682258-G-C is described in ClinVar as [Benign]. Clinvar id is 1245838.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPM2	NM_001301226.2	c.773-95C>G		intron_variant
TPM2	NM_213674.1	c.773-95C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPM2	ENST00000378292.9	c.773-95C>G		intron_variant		1
TPM2	ENST00000644325.1	c.*450C>G		3_prime_UTR_variant	4/4
TPM2	ENST00000329305.6	c.773-95C>G		intron_variant		2		A1
TPM2	ENST00000643485.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29387 AN: 151990 Hom.: 3374 Cov.: 32

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.229 AC: 269605 AN: 1179034 Hom.: 33127 Cov.: 16 AF XY: 0.232 AC XY: 137960 AN XY: 595744

Gnomad4 AFR exome AF: 0.0710

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.0593

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.193 AC: 29405 AN: 152108 Hom.: 3381 Cov.: 32 AF XY: 0.196 AC XY: 14566 AN XY: 74364

Gnomad4 AFR AF: 0.0728

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0590

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.214

Alfa AF: 0.139 Hom.: 306

Bravo AF: 0.185

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.50

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: rs10972558; hg19: chr9-35682255; COSMIC: COSV61407586; COSMIC: COSV61407586;