Genetic Variant TRAPPC2:c.*1848dupA (chrX-13712558-A-AT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001011658.4(TRAPPC2):c.*1848dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00784 in 112,389 control chromosomes in the GnomAD database, including 4 homozygotes. There are 257 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 4 hom., 257 hem., cov: 23)

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

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.263

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-13712558-A-AT is Benign according to our data. Variant chrX-13712558-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 367967.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00784 (881/112389) while in subpopulation AFR AF= 0.0232 (718/30951). AF 95% confidence interval is 0.0218. There are 4 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4 link	c.*1848dupA		3_prime_UTR_variant	Exon 6 of 6	ENST00000380579.6	NP_001011658.1	P0DI81-1P0DI82Q6IBE5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAPPC2	ENST00000380579 link	c.*1848dupA	3_prime_UTR_variant	Exon 6 of 6	1	NM_001011658.4	ENSP00000369953.1	P0DI81-1
TRAPPC2	ENST00000683983 link	c.*1848dupA	3_prime_UTR_variant	Exon 6 of 6			ENSP00000507474.1	P0DI81-3
TRAPPC2	ENST00000359680 link	c.*1848dupA	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352708.5	P0DI81-1
TRAPPC2	ENST00000683569 link	c.*1848dupA	3_prime_UTR_variant	Exon 7 of 7			ENSP00000508155.1	P0DI81-1

Frequencies

GnomAD3 genomes

AF:

0.00784

AC:

881

AN:

112336

Hom.:

Cov.:

AF XY:

0.00745

AC XY:

257

AN XY:

34492

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00245

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0188

Gnomad SAS

AF:

0.0208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00332

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

AF:

0.00784

AC:

881

AN:

112389

Hom.:

Cov.:

AF XY:

0.00744

AC XY:

257

AN XY:

34555

show subpopulations

Gnomad4 AFR

AF:

0.0232

Gnomad4 AMR

AF:

0.00245

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0186

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00393

Alfa

AF:

0.00569

Hom.:

Bravo

AF:

0.00886

Asia WGS

AF:

0.0250

AC:

AN:

2522

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spondyloepiphyseal dysplasia congenita

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over