9-35682350-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000378292.9(TPM2):c.773-187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 947,914 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (13 hom.)
• Consequence: TPM2 ENST00000378292.9 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.36

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=-0.92).
• BP6: Variant 9-35682350-G-A is Benign according to our data. Variant chr9-35682350-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1205261.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00435 (662/152296) while in subpopulation NFE AF= 0.00373 (254/68016). AF 95% confidence interval is 0.00336. There are 5 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 663 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPM2	NM_001301226.2	c.773-187C>T		intron_variant
TPM2	NM_213674.1	c.773-187C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPM2	ENST00000378292.9	c.773-187C>T		intron_variant		1
TPM2	ENST00000644325.1	c.*358C>T		3_prime_UTR_variant	4/4
TPM2	ENST00000329305.6	c.773-187C>T		intron_variant		2		A1
TPM2	ENST00000643485.1	n.1499C>T		non_coding_transcript_exon_variant	8/8

Frequencies

GnomAD3 genomes AF: 0.00436 AC: 663 AN: 152178 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00373

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00353 AC: 2812 AN: 795618 Hom.: 13 Cov.: 11 AF XY: 0.00327 AC XY: 1329 AN XY: 406426

Gnomad4 AFR exome AF: 0.000492

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.000157

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000395

Gnomad4 FIN exome AF: 0.0194

Gnomad4 NFE exome AF: 0.00356

Gnomad4 OTH exome AF: 0.00307

GnomAD4 genome AF: 0.00435 AC: 662 AN: 152296 Hom.: 5 Cov.: 32 AF XY: 0.00567 AC XY: 422 AN XY: 74478

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.00373

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00334 Hom.: 1

Bravo AF: 0.00240

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.12
Dann	Benign	0.60

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: rs145114937; hg19: chr9-35682347;