chr14-102376439-A-G

Position:

• chr14-102376439-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECPR2	NM_014844.5	c.-72-211A>G		intron_variant		ENST00000359520.12	NP_055659.2
TECPR2	NM_001172631.3	c.-72-211A>G		intron_variant			NP_001166102.1
LOC124903389	XR_007064350.1	n.73-5954T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECPR2	ENST00000359520.12	c.-72-211A>G		intron_variant		1	NM_014844.5	ENSP00000352510.7
TECPR2	ENST00000558678.1	c.-72-211A>G		intron_variant		1		ENSP00000453671.1
TECPR2	ENST00000561228.1	n.57-211A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.00739

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.0341

Gnomad4 SAS AF: 0.0428

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0270 Hom.: 9

Bravo AF: 0.0263

Asia WGS AF: 0.0450 AC: 155 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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	-0.83
CADD	Benign	0.76
DANN	Benign	0.51

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: rs17588387; hg19: chr14-102842776;