9-35684825-CG-CGGG

Position:

• chr9-35684825-CG-CGGG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_003289.4(TPM2):​c.564-19_564-18insCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,594,158 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (10 hom.)
• Consequence: TPM2 NM_003289.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39

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 -16 ACMG points.

• BP6: Variant 9-35684825-C-CGG is Benign according to our data. Variant chr9-35684825-C-CGG is described in ClinVar as [Likely_benign]. Clinvar id is 1565934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00193 (291/150634) while in subpopulation EAS AF= 0.012 (61/5084). AF 95% confidence interval is 0.00959. There are 4 homozygotes in gnomad4. There are 148 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 291 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPM2	NM_003289.4	c.564-19_564-18insCC		intron_variant		ENST00000645482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPM2	ENST00000645482.3	c.564-19_564-18insCC		intron_variant			NM_003289.4	A1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 288 AN: 150518 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.000663

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.00698

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.00485

GnomAD4 exome AF: 0.00191 AC: 2754 AN: 1443524 Hom.: 10 Cov.: 36 AF XY: 0.00191 AC XY: 1371 AN XY: 717934

Gnomad4 AFR exome AF: 0.000697

Gnomad4 AMR exome AF: 0.00209

Gnomad4 ASJ exome AF: 0.00117

Gnomad4 EAS exome AF: 0.0143

Gnomad4 SAS exome AF: 0.00233

Gnomad4 FIN exome AF: 0.00779

Gnomad4 NFE exome AF: 0.00115

Gnomad4 OTH exome AF: 0.00283

GnomAD4 genome AF: 0.00193 AC: 291 AN: 150634 Hom.: 4 Cov.: 0 AF XY: 0.00201 AC XY: 148 AN XY: 73496

Gnomad4 AFR AF: 0.000661

Gnomad4 AMR AF: 0.00172

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.00698

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.00625

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Arthrogryposis, distal, type 1A;C0546264:Congenital myopathy with fiber type disproportion;C1836447:Congenital myopathy 23 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 06, 2022

- -

Arthrogryposis, distal, type 1A Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3215700; hg19: chr9-35684822;