chr14-102428245-G-A

Variant names:

• chr14-102428245-G-A
• rs55716270
• NM_014844.5:c.952-5G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014844.5(TECPR2):​c.952-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0057 (30 hom.)
• Consequence: TECPR2 NM_014844.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004091
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.377
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 14-102428245-G-A is Benign according to our data. Variant chr14-102428245-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 240925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00848 (226/26640) while in subpopulation NFE AF = 0.0136 (173/12714). AF 95% confidence interval is 0.012. There are 0 homozygotes in GnomAd4. There are 102 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 30 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.952-5G>A		splice_region intron	N/A	NP_055659.2	O15040-1
	TECPR2	NM_001172631.3		c.952-5G>A		splice_region 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.952-5G>A		splice_region intron	N/A	ENSP00000352510.7	O15040-1
	TECPR2	ENST00000558678.1	TSL:1	c.952-5G>A		splice_region intron	N/A	ENSP00000453671.1	O15040-2
	TECPR2	ENST00000856897.1		c.952-5G>A		splice_region intron	N/A	ENSP00000526956.1

Frequencies

GnomAD3 genomes AF: 0.00849 AC: 226 AN: 26624 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00264

Gnomad AMI AF: 0.0988

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0109

GnomAD2 exomes AF: 0.00348 AC: 76 AN: 21844 AF XY: 0.00400

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00140

Gnomad NFE exome AF: 0.00469

Gnomad OTH exome AF: 0.00922

GnomAD4 exome AF: 0.00566 AC: 3204 AN: 565598 Hom.: 30 Cov.: 17 AF XY: 0.00541 AC XY: 1489 AN XY: 275256

African (AFR) AF: 0.000489 AC: 6 AN: 12272

American (AMR) AF: 0.00257 AC: 18 AN: 6992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9446

East Asian (EAS) AF: 0.00 AC: 0 AN: 18878

South Asian (SAS) AF: 0.000133 AC: 2 AN: 15014

European-Finnish (FIN) AF: 0.00114 AC: 25 AN: 21958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1870

European-Non Finnish (NFE) AF: 0.00668 AC: 3035 AN: 454516

Other (OTH) AF: 0.00479 AC: 118 AN: 24652

GnomAD4 genome AF: 0.00848 AC: 226 AN: 26640 Hom.: 0 Cov.: 0 AF XY: 0.00797 AC XY: 102 AN XY: 12790

African (AFR) AF: 0.00263 AC: 19 AN: 7222

American (AMR) AF: 0.00463 AC: 11 AN: 2374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 656

East Asian (EAS) AF: 0.00 AC: 0 AN: 1114

South Asian (SAS) AF: 0.00 AC: 0 AN: 922

European-Finnish (FIN) AF: 0.00189 AC: 2 AN: 1058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 30

European-Non Finnish (NFE) AF: 0.0136 AC: 173 AN: 12714

Other (OTH) AF: 0.0106 AC: 4 AN: 378

Alfa AF: 0.000920 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 (1)
-	-	1	Hereditary spastic paraplegia 49 (1)
-	-	1	TECPR2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.3
DANN	Benign	0.75
PhyloP100		-0.38
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.0
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: rs55716270; hg19: chr14-102894582;