rs17588387

Variant names:

• chr14-102376439-A-G
• rs17588387
• NM_014844.5:c.-72-211A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014844.5(TECPR2):​c.-72-211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 152,272 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.027 (74 hom., cov: 32)
• Consequence: TECPR2 NM_014844.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.100
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-102376439-A-G is Benign according to our data. Variant chr14-102376439-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 672764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0272 (4144/152272) while in subpopulation SAS AF = 0.0428 (206/4818). AF 95% confidence interval is 0.038. There are 74 homozygotes in GnomAd4. There are 2055 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 74 AR gene

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.-72-211A>G		intron	N/A	NP_055659.2	O15040-1
	TECPR2	NM_001172631.3		c.-72-211A>G		intron	N/A	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.-72-211A>G		intron	N/A	ENSP00000352510.7	O15040-1
	TECPR2	ENST00000558678.1	TSL:1	c.-72-211A>G		intron	N/A	ENSP00000453671.1	O15040-2
	TECPR2	ENST00000856897.1		c.-72-211A>G		intron	N/A	ENSP00000526956.1

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 4144 AN: 152154 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.00741

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0272 AC: 4144 AN: 152272 Hom.: 74 Cov.: 32 AF XY: 0.0276 AC XY: 2055 AN XY: 74458

African (AFR) AF: 0.00739 AC: 307 AN: 41550

American (AMR) AF: 0.0384 AC: 587 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3472

East Asian (EAS) AF: 0.0341 AC: 177 AN: 5188

South Asian (SAS) AF: 0.0428 AC: 206 AN: 4818

European-Finnish (FIN) AF: 0.0406 AC: 430 AN: 10604

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0312 AC: 2123 AN: 68034

Other (OTH) AF: 0.0407 AC: 86 AN: 2112

Alfa AF: 0.0270 Hom.: 9

Bravo AF: 0.0263

Asia WGS AF: 0.0450 AC: 155 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.76
DANN	Benign	0.51
PhyloP100		0.10
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

Other links and lift over

dbSNP: rs17588387; hg19: chr14-102842776;