7-102554443-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001396242.1(SPDYE2):​c.245C>T​(p.Pro82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000012 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SPDYE2
NM_001396242.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.653
Variant links:
Genes affected
SPDYE2 (HGNC:33841): (speedy/RINGO cell cycle regulator family member E2) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]
POLR2J3 (HGNC:33853): (RNA polymerase II subunit J3) This gene is a member of the RNA polymerase II subunit 11 gene family, which includes three genes in a cluster on chromosome 7q22.1 and a pseudogene on chromosome 7p13. The founding member of this family, DNA directed RNA polymerase II polypeptide J, has been shown to encode a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This locus produces multiple, alternatively spliced transcripts that potentially express isoforms with distinct C-termini compared to DNA directed RNA polymerase II polypeptide J. Most or all variants are spliced to include additional non-coding exons at the 3' end which makes them candidates for nonsense-mediated decay (NMD). Consequently, it is not known if this locus expresses a protein or proteins in vivo. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05838579).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPDYE2NM_001396242.1 linkc.245C>T p.Pro82Leu missense_variant Exon 3 of 9 ENST00000691607.2 NP_001383171.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPDYE2ENST00000691607.2 linkc.245C>T p.Pro82Leu missense_variant Exon 3 of 9 NM_001396242.1 ENSP00000509749.1 Q495Y8-1
ENSG00000270249ENST00000514917.3 linkc.748+12139G>A intron_variant Intron 6 of 6 3 ENSP00000423309.4 H0Y980
POLR2J3ENST00000513506.6 linkc.382+12139G>A intron_variant Intron 4 of 6 5 ENSP00000421085.1 E7EWC6

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151988
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000196
AC:
1
AN:
51026
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
25686
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000135
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000118
AC:
17
AN:
1441676
Hom.:
0
Cov.:
38
AF XY:
0.0000139
AC XY:
10
AN XY:
717276
show subpopulations
Gnomad4 AFR exome
AF:
0.0000600
Gnomad4 AMR exome
AF:
0.0000228
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.0000466
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000451
Gnomad4 OTH exome
AF:
0.0000666
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000131
AC:
2
AN:
152106
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.245C>T (p.P82L) alteration is located in exon 3 (coding exon 2) of the SPDYE2 gene. This alteration results from a C to T substitution at nucleotide position 245, causing the proline (P) at amino acid position 82 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
5.9
DANN
Benign
0.48
DEOGEN2
Benign
0.070
T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.35
.;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.058
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.53
N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-3.2
D;.
REVEL
Benign
0.028
Sift
Benign
0.33
T;.
Sift4G
Benign
0.12
T;T
Polyphen
0.0080
B;B
Vest4
0.17
MutPred
0.17
Loss of loop (P = 0.0084);Loss of loop (P = 0.0084);
MVP
0.11
ClinPred
0.051
T
Varity_R
0.070
gMVP
0.022

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1438765775; hg19: chr7-102194890; API