9-35684825-CG-CGG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003289.4(TPM2):​c.564-19dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,596,748 control chromosomes in the GnomAD database, including 303,763 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29446 hom., cov: 0)
Exomes 𝑓: 0.62 ( 274317 hom. )

Consequence

TPM2
NM_003289.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.39
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 9-35684825-C-CG is Benign according to our data. Variant chr9-35684825-C-CG is described in ClinVar as [Benign]. Clinvar id is 94123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TPM2NM_003289.4 linkuse as main transcriptc.564-19dupC intron_variant ENST00000645482.3 NP_003280.2 P07951-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TPM2ENST00000645482.3 linkuse as main transcriptc.564-19dupC intron_variant NM_003289.4 ENSP00000496494.2 P07951-1

Frequencies

GnomAD3 genomes
AF:
0.624
AC:
93834
AN:
150344
Hom.:
29415
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.596
Gnomad AMI
AF:
0.558
Gnomad AMR
AF:
0.628
Gnomad ASJ
AF:
0.608
Gnomad EAS
AF:
0.640
Gnomad SAS
AF:
0.707
Gnomad FIN
AF:
0.705
Gnomad MID
AF:
0.554
Gnomad NFE
AF:
0.622
Gnomad OTH
AF:
0.644
GnomAD4 exome
AF:
0.618
AC:
893752
AN:
1446288
Hom.:
274317
Cov.:
36
AF XY:
0.620
AC XY:
446208
AN XY:
719346
show subpopulations
Gnomad4 AFR exome
AF:
0.587
Gnomad4 AMR exome
AF:
0.620
Gnomad4 ASJ exome
AF:
0.611
Gnomad4 EAS exome
AF:
0.631
Gnomad4 SAS exome
AF:
0.694
Gnomad4 FIN exome
AF:
0.682
Gnomad4 NFE exome
AF:
0.609
Gnomad4 OTH exome
AF:
0.617
GnomAD4 genome
AF:
0.624
AC:
93917
AN:
150460
Hom.:
29446
Cov.:
0
AF XY:
0.629
AC XY:
46210
AN XY:
73418
show subpopulations
Gnomad4 AFR
AF:
0.596
Gnomad4 AMR
AF:
0.629
Gnomad4 ASJ
AF:
0.608
Gnomad4 EAS
AF:
0.640
Gnomad4 SAS
AF:
0.708
Gnomad4 FIN
AF:
0.705
Gnomad4 NFE
AF:
0.622
Gnomad4 OTH
AF:
0.645

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, no assertion criteria providedclinical testingEurofins Ntd Llc (ga)Oct 18, 2012- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingGeneDxFeb 24, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Arthrogryposis, distal, type 1A Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3215700; hg19: chr9-35684822; API