rs2296145

Variant names:

• chr14-102376702-A-C
• rs2296145
• NM_014844.5:c.-20A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014844.5(TECPR2):​c.-20A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 1,608,772 control chromosomes in the GnomAD database, including 1,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (138 hom., cov: 32)
  • Exomes 𝑓: 0.033 (942 hom.)
• Consequence: TECPR2 NM_014844.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0210
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-102376702-A-C is Benign according to our data. Variant chr14-102376702-A-C is described in ClinVar as Benign. ClinVar VariationId is 380926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0578 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.-20A>C		5_prime_UTR	Exon 2 of 20	NP_055659.2	O15040-1
	TECPR2	NM_001172631.3		c.-20A>C		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.-20A>C		5_prime_UTR	Exon 2 of 20	ENSP00000352510.7	O15040-1
	TECPR2	ENST00000558678.1	TSL:1	c.-20A>C		5_prime_UTR	Exon 2 of 17	ENSP00000453671.1	O15040-2
	TECPR2	ENST00000856897.1		c.-20A>C		5_prime_UTR	Exon 2 of 20	ENSP00000526956.1

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6068 AN: 152142 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0313

Gnomad OTH AF: 0.0503

GnomAD2 exomes AF: 0.0385 AC: 9665 AN: 251054 AF XY: 0.0375

Gnomad AFR exome AF: 0.0523

Gnomad AMR exome AF: 0.0621

Gnomad ASJ exome AF: 0.0484

Gnomad EAS exome AF: 0.0289

Gnomad FIN exome AF: 0.0377

Gnomad NFE exome AF: 0.0305

Gnomad OTH exome AF: 0.0397

GnomAD4 exome AF: 0.0334 AC: 48676 AN: 1456512 Hom.: 942 Cov.: 30 AF XY: 0.0332 AC XY: 24094 AN XY: 724950

African (AFR) AF: 0.0478 AC: 1596 AN: 33378

American (AMR) AF: 0.0597 AC: 2669 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0469 AC: 1224 AN: 26094

East Asian (EAS) AF: 0.0401 AC: 1591 AN: 39678

South Asian (SAS) AF: 0.0382 AC: 3285 AN: 86104

European-Finnish (FIN) AF: 0.0390 AC: 2081 AN: 53408

Middle Eastern (MID) AF: 0.0524 AC: 302 AN: 5760

European-Non Finnish (NFE) AF: 0.0305 AC: 33821 AN: 1107174

Other (OTH) AF: 0.0350 AC: 2107 AN: 60224

GnomAD4 genome AF: 0.0398 AC: 6067 AN: 152260 Hom.: 138 Cov.: 32 AF XY: 0.0398 AC XY: 2960 AN XY: 74438

African (AFR) AF: 0.0508 AC: 2112 AN: 41558

American (AMR) AF: 0.0442 AC: 675 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 158 AN: 3468

East Asian (EAS) AF: 0.0340 AC: 176 AN: 5180

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4830

European-Finnish (FIN) AF: 0.0408 AC: 433 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0313 AC: 2129 AN: 68016

Other (OTH) AF: 0.0508 AC: 107 AN: 2108

Alfa AF: 0.0363 Hom.: 75

Bravo AF: 0.0411

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.4
DANN	Benign	0.46
PhyloP100		0.021
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs2296145; hg19: chr14-102843039;