NM_139286.4:c.155G>A

Variant names:

• chr9-113267366-C-T
• rs775003535
• NM_139286.4:c.155G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139286.4(CDC26):​c.155G>A​(p.Ser52Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDC26 NM_139286.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.311
• Publications: 0 publications found

Genes affected

CDC26 (HGNC:17839): (cell division cycle 26) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc26, a component of cell cycle anaphase-promoting complex (APC). APC is composed of a group of highly conserved proteins and functions as a cell cycle-regulated ubiquitin-protein ligase. APC thus is responsible for the cell cycle regulated proteolysis of various proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05124536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139286.4. 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
	CDC26	NM_139286.4	MANE Select	c.155G>A	p.Ser52Asn	missense	Exon 4 of 4	NP_644815.1	Q8NHZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC26	ENST00000374206.4	TSL:1 MANE Select	c.155G>A	p.Ser52Asn	missense	Exon 4 of 4	ENSP00000363322.3	Q8NHZ8
	CDC26	ENST00000868464.1		c.155G>A	p.Ser52Asn	missense	Exon 4 of 4	ENSP00000538523.1
	CDC26	ENST00000868465.1		c.155G>A	p.Ser52Asn	missense	Exon 4 of 4	ENSP00000538524.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000138 AC: 2 AN: 1446918 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 719588

African (AFR) AF: 0.00 AC: 0 AN: 32642

American (AMR) AF: 0.00 AC: 0 AN: 41338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 83402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106288

Other (OTH) AF: 0.0000167 AC: 1 AN: 59712

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 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	Benign	0.074
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.31
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.039
Sift	Benign	0.22	T
Sift4G	Benign	0.075	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.32		Loss of phosphorylation at S52 (P = 0.0228)
MVP		0.11
MPC		1.0
ClinPred		0.59	D
GERP RS		1.4
Varity_R		0.049
gMVP		0.59
Mutation Taster		=89/11	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: rs775003535; hg19: chr9-116029646;