Genetic Variant SPDYE2B:p.Phe233Leu (chr7-102657580-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001166339.2(SPDYE2B):c.699C>G(p.Phe233Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 5)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPDYE2B
NM_001166339.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.126

Variant links:

Genes affected

SPDYE2B (HGNC:48334): (speedy/RINGO cell cycle regulator family member E2B) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SPDYE2B links:

ENSG00000267645 (HGNC:):

ENSG00000267645 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34146243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPDYE2B	NM_001166339.2 link	c.699C>G	p.Phe233Leu	missense_variant	Exon 6 of 9	ENST00000507450.6	NP_001159811.1	A6NHP3-1
SPDYE2B	XM_011515702.4 link	c.699C>G	p.Phe233Leu	missense_variant	Exon 5 of 6		XP_011514004.1
SPDYE2B	XM_047419693.1 link	c.669+1274C>G		intron_variant	Intron 4 of 4		XP_047275649.1
POLR2J2-UPK3BL1	NR_173352.1 link	n.464+8497G>C		intron_variant	Intron 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPDYE2B	ENST00000507450.6 link	c.699C>G	p.Phe233Leu	missense_variant	Exon 6 of 9	2	NM_001166339.2	ENSP00000424058.1		A6NHP3-1
ENSG00000267645	ENST00000476151.5 link	n.*54+8497G>C		intron_variant	Intron 4 of 8	1		ENSP00000418603.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

30218

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000165

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000114

AC:

AN:

351884

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

185202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000892

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000181

Gnomad4 OTH exome

AF:

0.0000492

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000662

AC:

AN:

30218

Hom.:

Cov.:

AF XY:

0.0000761

AC XY:

AN XY:

13146

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000165

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 19, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.699C>G (p.F233L) alteration is located in exon 6 (coding exon 5) of the SPDYE2B gene. This alteration results from a C to G substitution at nucleotide position 699, causing the phenylalanine (F) at amino acid position 233 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.37

T;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.85

.;D;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.9

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.46

MutPred

0.68

Loss of catalytic residue at F233 (P = 0.0833);Loss of catalytic residue at F233 (P = 0.0833);.;

MVP

0.014

ClinPred

0.98

Varity_R

0.50

gMVP

0.083

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over