rs564260248

Variant names:

• chr14-102428232-T-G
• rs564260248
• NM_014844.5:c.952-18T>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_014844.5(TECPR2):​c.952-18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 148,724 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00087 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00082 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: TECPR2 NM_014844.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0380
• 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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 14-102428232-T-G is Benign according to our data. Variant chr14-102428232-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 445658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000867 (129/148724) while in subpopulation EAS AF = 0.0169 (86/5090). AF 95% confidence interval is 0.014. There are 1 homozygotes in GnomAd4. There are 57 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

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.952-18T>G		intron	N/A	NP_055659.2	O15040-1
	TECPR2	NM_001172631.3		c.952-18T>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.952-18T>G		intron	N/A	ENSP00000352510.7	O15040-1
	TECPR2	ENST00000558678.1	TSL:1	c.952-18T>G		intron	N/A	ENSP00000453671.1	O15040-2
	TECPR2	ENST00000856897.1		c.952-18T>G		intron	N/A	ENSP00000526956.1

Frequencies

GnomAD3 genomes AF: 0.000875 AC: 130 AN: 148628 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000335

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000327

Gnomad OTH AF: 0.000494

GnomAD2 exomes AF: 0.00427 AC: 248 AN: 58120 AF XY: 0.00408

Gnomad AFR exome AF: 0.000203

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0347

Gnomad FIN exome AF: 0.000630

Gnomad NFE exome AF: 0.000863

Gnomad OTH exome AF: 0.00399

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000815 AC: 990 AN: 1214170 Hom.: 6 Cov.: 28 AF XY: 0.000798 AC XY: 469 AN XY: 587786

African (AFR) AF: 0.000197 AC: 5 AN: 25356

American (AMR) AF: 0.000655 AC: 9 AN: 13746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16176

East Asian (EAS) AF: 0.0155 AC: 473 AN: 30610

South Asian (SAS) AF: 0.000488 AC: 24 AN: 49194

European-Finnish (FIN) AF: 0.000374 AC: 14 AN: 37424

Middle Eastern (MID) AF: 0.00212 AC: 10 AN: 4724

European-Non Finnish (NFE) AF: 0.000424 AC: 419 AN: 987954

Other (OTH) AF: 0.000735 AC: 36 AN: 48986

GnomAD4 genome AF: 0.000867 AC: 129 AN: 148724 Hom.: 1 Cov.: 30 AF XY: 0.000786 AC XY: 57 AN XY: 72528

African (AFR) AF: 0.000295 AC: 12 AN: 40662

American (AMR) AF: 0.000334 AC: 5 AN: 14958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.0169 AC: 86 AN: 5090

South Asian (SAS) AF: 0.000426 AC: 2 AN: 4690

European-Finnish (FIN) AF: 0.000106 AC: 1 AN: 9468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000327 AC: 22 AN: 67176

Other (OTH) AF: 0.000490 AC: 1 AN: 2042

Alfa AF: 0.000409 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.37
DANN	Benign	0.59
PhyloP100		-0.038
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: rs564260248; hg19: chr14-102894569;