7-102554443-C-G

Variant names:

• chr7-102554443-C-G
• rs1438765775
• NM_001396242.1:c.245C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001396242.1(SPDYE2):​c.245C>G​(p.Pro82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P82L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 29)
• Consequence: SPDYE2 NM_001396242.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 0 publications found

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]

ENSG00000270249 (HGNC:):

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]

POLR2J3-UPK3BL2 (HGNC:58364):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16047782).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396242.1. 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
	SPDYE2	NM_001396242.1	MANE Select	c.245C>G	p.Pro82Arg	missense	Exon 3 of 9	NP_001383171.1	Q495Y8-1
	SPDYE2	NM_001031618.3		c.245C>G	p.Pro82Arg	missense	Exon 3 of 9	NP_001026789.2	Q495Y8-1
	POLR2J3-UPK3BL2	NR_173351.1		n.464+12554G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE2	ENST00000691607.2	MANE Select	c.245C>G	p.Pro82Arg	missense	Exon 3 of 9	ENSP00000509749.1	Q495Y8-1
	ENSG00000270249	ENST00000514917.3	TSL:3	c.748+12139G>C		intron	N/A	ENSP00000423309.4	H0Y980
	POLR2J3	ENST00000513506.6	TSL:5	c.382+12139G>C		intron	N/A	ENSP00000421085.1	E7EWC6

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.0
DANN	Benign	0.84
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.65
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.070
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.89	P
Vest4		0.18
MutPred		0.12		Loss of glycosylation at P82 (P = 0.0116)
MVP		0.17
ClinPred		0.38	T
Varity_R		0.21
gMVP		0.023
Mutation Taster		=300/0	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: rs1438765775; hg19: chr7-102194890;