rs3215700

Positions:

• chr9-35684825-CG-C
• chr9-35684825-CG-CGG
• chr9-35684825-CG-CGGG
• chr9-35684825-CG-CGGGG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_003289.4(TPM2):​c.564-19del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 1,597,284 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: TPM2 NM_003289.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 9-35684825-CG-C is Benign according to our data. Variant chr9-35684825-CG-C is described in ClinVar as [Benign]. Clinvar id is 1599464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-35684825-CG-C is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000731 AC: 11 AN: 150536 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000396

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000221 AC: 32 AN: 1446748 Hom.: 0 Cov.: 36 AF XY: 0.0000195 AC XY: 14 AN XY: 719592

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.0000459

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000254

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome AF: 0.0000731 AC: 11 AN: 150536 Hom.: 0 Cov.: 0 AF XY: 0.000123 AC XY: 9 AN XY: 73382

Gnomad4 AFR AF: 0.000123

Gnomad4 AMR AF: 0.000396

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Arthrogryposis, distal, type 1A Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

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: rs3215700; hg19: chr9-35684822;