Genetic Variant TRAPPC2:c.*1302_*1303dupTT (chrX-13713103-C-CAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001011658.4(TRAPPC2):c.*1302_*1303dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., 7 hem., cov: 5)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

TRAPPC2
NM_001011658.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.108

Publications

0 publications found

Variant links:

Genes affected

TRAPPC2 (HGNC:23068): (trafficking protein particle complex subunit 2) The protein encoded by this gene is thought to be part of a large multi-subunit complex involved in the targeting and fusion of endoplasmic reticulum-to-Golgi transport vesicles with their acceptor compartment. In addition, the encoded protein can bind c-myc promoter-binding protein 1 and block its transcriptional repression capability. Mutations in this gene are a cause of spondyloepiphyseal dysplasia tarda (SEDT). A processed pseudogene of this gene is located on chromosome 19, and other pseudogenes are found on chromosomes 8 and Y. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2010]

TRAPPC2 Gene-Disease associations (from GenCC):

spondyloepiphyseal dysplasia tarda, X-linked
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
spondyloepiphyseal dysplasia tarda
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRAPPC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00187 (129/68873) while in subpopulation AFR AF = 0.00658 (117/17777). AF 95% confidence interval is 0.00561. There are 2 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 5. This position passed quality control check.

BS2

High AC in GnomAd4 at 129 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011658.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAPPC2	NM_001011658.4	MANE Select	c.1302_1303dupTT	3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
TRAPPC2	NM_001128835.3		c.1302_1303dupTT	3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
TRAPPC2	NM_014563.6		c.1302_1303dupTT	3_prime_UTR	Exon 5 of 5	NP_055378.1	P0DI81-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAPPC2	ENST00000380579.6	TSL:1 MANE Select	c.1302_1303dupTT	3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
TRAPPC2	ENST00000683983.1		c.1302_1303dupTT	3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
TRAPPC2	ENST00000359680.9	TSL:1	c.1302_1303dupTT	3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

129

AN:

68894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00659

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000873

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000273

Gnomad OTH

AF:

0.00340

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

126

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

122

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.00187

AC:

129

AN:

68873

Hom.:

Cov.:

AF XY:

0.000617

AC XY:

AN XY:

11345

show subpopulations

African (AFR)

AF:

0.00658

AC:

117

AN:

17777

American (AMR)

AF:

0.00103

AC:

AN:

5826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1840

East Asian (EAS)

AF:

0.000877

AC:

AN:

2280

South Asian (SAS)

AF:

0.00

AC:

AN:

1278

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1829

Middle Eastern (MID)

AF:

0.00

AC:

AN:

123

European-Non Finnish (NFE)

AF:

0.0000273

AC:

AN:

36624

Other (OTH)

AF:

0.00336

AC:

AN:

894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over