14-102428232-T-G

Variant names:

• chr14-102428232-T-G
• rs564260248
• NM_014844.5:c.952-18T>G

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 30. This position FAILED quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECPR2	NM_014844.5	c.952-18T>G		intron_variant	Intron 6 of 19	ENST00000359520.12	NP_055659.2
TECPR2	NM_001172631.3	c.952-18T>G		intron_variant	Intron 6 of 16		NP_001166102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECPR2	ENST00000359520.12	c.952-18T>G		intron_variant	Intron 6 of 19	1	NM_014844.5	ENSP00000352510.7
TECPR2	ENST00000558678.1	c.952-18T>G		intron_variant	Intron 6 of 16	1		ENSP00000453671.1

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

GnomAD2 exomes AF: 0.00427 AC: 248 AN: 58120 AF XY: 0.00408

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 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 AC: 5 AN: 25356

Gnomad4 AMR exome AF: 0.000655 AC: 9 AN: 13746

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 16176

Gnomad4 EAS exome AF: 0.0155 AC: 473 AN: 30610

Gnomad4 SAS exome AF: 0.000488 AC: 24 AN: 49194

Gnomad4 FIN exome AF: 0.000374 AC: 14 AN: 37424

Gnomad4 NFE exome AF: 0.000424 AC: 419 AN: 987954

Gnomad4 Remaining exome AF: 0.000735 AC: 36 AN: 48986

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 AC: 0.000295116 AN: 0.000295116

Gnomad4 AMR AF: 0.000334 AC: 0.000334269 AN: 0.000334269

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.0169 AC: 0.0168959 AN: 0.0168959

Gnomad4 SAS AF: 0.000426 AC: 0.000426439 AN: 0.000426439

Gnomad4 FIN AF: 0.000106 AC: 0.000105619 AN: 0.000105619

Gnomad4 NFE AF: 0.000327 AC: 0.000327498 AN: 0.000327498

Gnomad4 OTH AF: 0.000490 AC: 0.000489716 AN: 0.000489716

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

Feb 15, 2022

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Jun 05, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia 49 Benign:1

Jan 16, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.37
DANN	Benign	0.59
Mutation Taster		=100/0	polymorphism

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;