9-35682299-T-A

Variant summary

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

The ENST00000378292.9(TPM2):c.773-136A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,043,166 control chromosomes in the GnomAD database, including 205,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (27626 hom., cov: 31)
  • Exomes 𝑓: 0.63 (178278 hom.)
• Consequence: TPM2 ENST00000378292.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.830

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=-0.91).
• BP6: Variant 9-35682299-T-A is Benign according to our data. Variant chr9-35682299-T-A is described in ClinVar as [Benign]. Clinvar id is 1269529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPM2	NM_001301226.2	c.773-136A>T		intron_variant
TPM2	NM_213674.1	c.773-136A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPM2	ENST00000378292.9	c.773-136A>T		intron_variant		1
TPM2	ENST00000644325.1	c.*409A>T		3_prime_UTR_variant	4/4
TPM2	ENST00000329305.6	c.773-136A>T		intron_variant		2		A1
TPM2	ENST00000643485.1	n.1550A>T		non_coding_transcript_exon_variant	8/8

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90835 AN: 151848 Hom.: 27591 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.627 AC: 558587 AN: 891200 Hom.: 178278 Cov.: 12 AF XY: 0.626 AC XY: 286759 AN XY: 457978

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.693

Gnomad4 ASJ exome AF: 0.628

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.589

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.653

Gnomad4 OTH exome AF: 0.622

GnomAD4 genome AF: 0.598 AC: 90915 AN: 151966 Hom.: 27626 Cov.: 31 AF XY: 0.593 AC XY: 44085 AN XY: 74288

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.596

Alfa AF: 0.509 Hom.: 1417

Bravo AF: 0.602

Asia WGS AF: 0.465 AC: 1617 AN: 3476

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 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.16
Dann	Benign	0.62

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: rs11998; hg19: chr9-35682296;