14-102376702-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.0210

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]

LOC124903389 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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 id is 380926.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102376702-A-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECPR2	NM_014844.5	c.-20A>C		5_prime_UTR_variant	2/20	ENST00000359520.12
LOC124903389	XR_007064350.1	n.73-6217T>G		intron_variant, non_coding_transcript_variant
TECPR2	NM_001172631.3	c.-20A>C		5_prime_UTR_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECPR2	ENST00000359520.12	c.-20A>C		5_prime_UTR_variant	2/20	1	NM_014844.5	P1
TECPR2	ENST00000558678.1	c.-20A>C		5_prime_UTR_variant	2/17	1
TECPR2	ENST00000561228.1	n.109A>C		non_coding_transcript_exon_variant	2/6	2

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

GnomAD3 exomes AF: 0.0385 AC: 9665 AN: 251054 Hom.: 241 AF XY: 0.0375 AC XY: 5082 AN XY: 135688

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 SAS exome AF: 0.0370

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

Gnomad4 AFR exome AF: 0.0478

Gnomad4 AMR exome AF: 0.0597

Gnomad4 ASJ exome AF: 0.0469

Gnomad4 EAS exome AF: 0.0401

Gnomad4 SAS exome AF: 0.0382

Gnomad4 FIN exome AF: 0.0390

Gnomad4 NFE exome AF: 0.0305

Gnomad4 OTH exome AF: 0.0350

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

Gnomad4 AFR AF: 0.0508

Gnomad4 AMR AF: 0.0442

Gnomad4 ASJ AF: 0.0456

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0313

Gnomad4 OTH AF: 0.0508

Alfa AF: 0.0356 Hom.: 62

Bravo AF: 0.0411

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 15, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	8.4
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs2296145; hg19: chr14-102843039;