rs1256244930

Variant names:

• chr7-102656299-C-T
• rs1256244930
• NM_001166339.2:c.662C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001166339.2(SPDYE2B):​c.662C>T​(p.Ser221Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 4)
  • Exomes 𝑓: 0.0000068 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE2B NM_001166339.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

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]

POLR2J2-UPK3BL1 (HGNC:58364):

ENSG00000279168 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37167662).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166339.2. 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
	SPDYE2B	NM_001166339.2	MANE Select	c.662C>T	p.Ser221Leu	missense	Exon 5 of 9	NP_001159811.1	A6NHP3-1
	POLR2J2-UPK3BL1	NR_173352.1		n.464+9778G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE2B	ENST00000507450.6	TSL:2 MANE Select	c.662C>T	p.Ser221Leu	missense	Exon 5 of 9	ENSP00000424058.1	A6NHP3-1
	SPDYE2B	ENST00000436228.6	TSL:1	c.662C>T	p.Ser221Leu	missense	Exon 4 of 7	ENSP00000440393.1	A6NHP3-1
	SPDYE2B	ENST00000455020.3	TSL:1	c.230C>T	p.Ser77Leu	missense	Exon 2 of 6	ENSP00000414338.2	A6NHP3-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 22796 Hom.: 0 Cov.: 4

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000141 AC: 1 AN: 71094 AF XY: 0.0000280

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000512

Gnomad EAS 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: 0.00000684 AC: 2 AN: 292346 Hom.: 0 Cov.: 2 AF XY: 0.0000125 AC XY: 2 AN XY: 159638

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14616

American (AMR) AF: 0.00 AC: 0 AN: 14424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6392

East Asian (EAS) AF: 0.00 AC: 0 AN: 22992

South Asian (SAS) AF: 0.0000248 AC: 1 AN: 40392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1014

European-Non Finnish (NFE) AF: 0.00000624 AC: 1 AN: 160314

Other (OTH) AF: 0.00 AC: 0 AN: 15268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 22796 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 10628

African (AFR) AF: 0.00 AC: 0 AN: 15536

American (AMR) AF: 0.00 AC: 0 AN: 1378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 212

East Asian (EAS) AF: 0.00 AC: 0 AN: 698

South Asian (SAS) AF: 0.00 AC: 0 AN: 172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4248

Other (OTH) AF: 0.00 AC: 0 AN: 208

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.0059	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.034	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.084
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.47		Loss of ubiquitination at K216 (P = 0.064)
MVP		0.14
ClinPred		0.81	D
Varity_R		0.61
gMVP		0.19
Mutation Taster		=99/1	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: rs1256244930; hg19: chr7-102296746;