14-102402141-T-C

Variant names:

• chr14-102402141-T-C
• rs12434098
• NM_014844.5:c.220-5197T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014844.5(TECPR2):​c.220-5197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,070 control chromosomes in the GnomAD database, including 10,352 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10352 hom., cov: 32)
• Consequence: TECPR2 NM_014844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 5 publications found

Genes affected

TECPR2 (HGNC:19957): (tectonin beta-propeller repeat containing 2) The protein encoded by this gene is a member of the tectonin beta-propeller repeat-containing (TECPR) family, and contains both TECPR and tryptophan-aspartic acid repeat (WD repeat) domains. This gene has been implicated in autophagy, as reduced expression levels of this gene have been associated with impaired autophagy. Recessive mutations in this gene have been associated with a hereditary form of spastic paraparesis (HSP). HSP is characterized by progressive spasticity and paralysis of the legs. There is also some evidence linking mutations in this gene with birdshot chorioretinopathy (BSCR), which results in inflammation of the choroid and retina. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

TECPR2 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 49

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014844.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECPR2	NM_014844.5	MANE Select	c.220-5197T>C		intron	N/A	NP_055659.2
	TECPR2	NM_001172631.3		c.220-5197T>C		intron	N/A	NP_001166102.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECPR2	ENST00000359520.12	TSL:1 MANE Select	c.220-5197T>C		intron	N/A	ENSP00000352510.7
	TECPR2	ENST00000558678.1	TSL:1	c.220-5197T>C		intron	N/A	ENSP00000453671.1
	TECPR2	ENST00000561228.1	TSL:2	n.348-5197T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55434 AN: 151952 Hom.: 10344 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.389

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55470 AN: 152070 Hom.: 10352 Cov.: 32 AF XY: 0.358 AC XY: 26641 AN XY: 74360

African (AFR) AF: 0.338 AC: 14010 AN: 41504

American (AMR) AF: 0.328 AC: 5001 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1611 AN: 3470

East Asian (EAS) AF: 0.179 AC: 925 AN: 5176

South Asian (SAS) AF: 0.352 AC: 1692 AN: 4812

European-Finnish (FIN) AF: 0.289 AC: 3047 AN: 10560

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27962 AN: 67972

Other (OTH) AF: 0.385 AC: 810 AN: 2106

Alfa AF: 0.395 Hom.: 2446

Bravo AF: 0.362

Asia WGS AF: 0.279 AC: 972 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.92
DANN	Benign	0.54
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12434098; hg19: chr14-102868478;