14-102376720-C-T

Variant names:

• chr14-102376720-C-T
• rs17100874
• NM_014844.5:c.-2C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_014844.5(TECPR2):​c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,613,746 control chromosomes in the GnomAD database, including 1,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (88 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1169 hom.)
• Consequence: TECPR2 NM_014844.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.37
• 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000308837 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 14-102376720-C-T is Benign according to our data. Variant chr14-102376720-C-T is described in ClinVar as Benign. ClinVar VariationId is 380941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0886 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECPR2	NM_014844.5	MANE Select	c.-2C>T		5_prime_UTR	Exon 2 of 20	NP_055659.2	O15040-1
	TECPR2	NM_001172631.3		c.-2C>T		5_prime_UTR	Exon 2 of 17	NP_001166102.1	O15040-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECPR2	ENST00000359520.12	TSL:1 MANE Select	c.-2C>T		5_prime_UTR	Exon 2 of 20	ENSP00000352510.7	O15040-1
	TECPR2	ENST00000558678.1	TSL:1	c.-2C>T		5_prime_UTR	Exon 2 of 17	ENSP00000453671.1	O15040-2
	TECPR2	ENST00000856897.1		c.-2C>T		5_prime_UTR	Exon 2 of 20	ENSP00000526956.1

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4014 AN: 152192 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0259

GnomAD2 exomes AF: 0.0343 AC: 8609 AN: 251314 AF XY: 0.0393

Gnomad AFR exome AF: 0.00953

Gnomad AMR exome AF: 0.0153

Gnomad ASJ exome AF: 0.0270

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.0248

Gnomad NFE exome AF: 0.0346

Gnomad OTH exome AF: 0.0308

GnomAD4 exome AF: 0.0340 AC: 49761 AN: 1461436 Hom.: 1169 Cov.: 31 AF XY: 0.0364 AC XY: 26486 AN XY: 727032

African (AFR) AF: 0.0110 AC: 367 AN: 33472

American (AMR) AF: 0.0161 AC: 718 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0278 AC: 726 AN: 26134

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.0984 AC: 8488 AN: 86234

European-Finnish (FIN) AF: 0.0237 AC: 1267 AN: 53414

Middle Eastern (MID) AF: 0.0512 AC: 295 AN: 5766

European-Non Finnish (NFE) AF: 0.0323 AC: 35901 AN: 1111606

Other (OTH) AF: 0.0330 AC: 1992 AN: 60390

GnomAD4 genome AF: 0.0264 AC: 4014 AN: 152310 Hom.: 88 Cov.: 32 AF XY: 0.0274 AC XY: 2037 AN XY: 74476

African (AFR) AF: 0.0110 AC: 457 AN: 41572

American (AMR) AF: 0.0249 AC: 381 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0958 AC: 462 AN: 4824

European-Finnish (FIN) AF: 0.0232 AC: 246 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0335 AC: 2280 AN: 68024

Other (OTH) AF: 0.0256 AC: 54 AN: 2110

Alfa AF: 0.0308 Hom.: 58

Bravo AF: 0.0237

Asia WGS AF: 0.0400 AC: 141 AN: 3478

EpiCase AF: 0.0348

EpiControl AF: 0.0323

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary spastic paraplegia 49 (2)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		3.4
Mutation Taster		=300/0	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: rs17100874; hg19: chr14-102843057;