rs564260248

Positions:

• chr14-102428232-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_014844.5(TECPR2):​c.952-18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 148,724 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00087 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00082 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: TECPR2 NM_014844.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0380

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 14-102428232-T-G is Benign according to our data. Variant chr14-102428232-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 445658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102428232-T-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000867 (129/148724) while in subpopulation EAS AF= 0.0169 (86/5090). AF 95% confidence interval is 0.014. There are 1 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECPR2	NM_014844.5	c.952-18T>G		intron_variant		ENST00000359520.12
TECPR2	NM_001172631.3	c.952-18T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECPR2	ENST00000359520.12	c.952-18T>G		intron_variant		1	NM_014844.5	P1
TECPR2	ENST00000558678.1	c.952-18T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.000875 AC: 130 AN: 148628 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000335

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000327

Gnomad OTH AF: 0.000494

GnomAD3 exomes AF: 0.00427 AC: 248 AN: 58120 Hom.: 1 AF XY: 0.00408 AC XY: 118 AN XY: 28928

Gnomad AFR exome AF: 0.000203

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0347

Gnomad SAS exome AF: 0.00104

Gnomad FIN exome AF: 0.000630

Gnomad NFE exome AF: 0.000863

Gnomad OTH exome AF: 0.00399

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000815 AC: 990 AN: 1214170 Hom.: 6 Cov.: 28 AF XY: 0.000798 AC XY: 469 AN XY: 587786

Gnomad4 AFR exome AF: 0.000197

Gnomad4 AMR exome AF: 0.000655

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.000488

Gnomad4 FIN exome AF: 0.000374

Gnomad4 NFE exome AF: 0.000424

Gnomad4 OTH exome AF: 0.000735

GnomAD4 genome AF: 0.000867 AC: 129 AN: 148724 Hom.: 1 Cov.: 30 AF XY: 0.000786 AC XY: 57 AN XY: 72528

Gnomad4 AFR AF: 0.000295

Gnomad4 AMR AF: 0.000334

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0169

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.000106

Gnomad4 NFE AF: 0.000327

Gnomad4 OTH AF: 0.000490

Alfa AF: 0.000409 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 15, 2022	See Variant Classification Assertion Criteria. -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 05, 2017	- -

Hereditary spastic paraplegia 49 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.37
DANN	Benign	0.59

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: rs564260248; hg19: chr14-102894569;