NM_001284240.2:c.679T>A

Variant names:

• chr10-84371731-T-A
• NM_001284240.2:c.679T>A

Variant summary

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

The NM_001284240.2(CCSER2):​c.679T>A​(p.Ser227Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCSER2 NM_001284240.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.28
• Publications: 0 publications found

Genes affected

CCSER2 (HGNC:29197): (coiled-coil serine rich protein 2) Predicted to enable microtubule binding activity. Predicted to act upstream of or within microtubule bundle formation. Predicted to be located in cytoplasm and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284240.2. 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
	CCSER2	NM_001284240.2	MANE Select	c.679T>A	p.Ser227Thr	missense	Exon 2 of 10	NP_001271169.1	Q9H7U1-3
	CCSER2	NM_001351290.2		c.679T>A	p.Ser227Thr	missense	Exon 2 of 12	NP_001338219.1
	CCSER2	NM_001351292.2		c.679T>A	p.Ser227Thr	missense	Exon 2 of 12	NP_001338221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCSER2	ENST00000372088.8	TSL:2 MANE Select	c.679T>A	p.Ser227Thr	missense	Exon 2 of 10	ENSP00000361160.2	Q9H7U1-3
	CCSER2	ENST00000359979.8	TSL:1	c.679T>A	p.Ser227Thr	missense	Exon 2 of 3	ENSP00000353068.4	Q9H7U1-2
	CCSER2	ENST00000898573.1		c.679T>A	p.Ser227Thr	missense	Exon 2 of 7	ENSP00000568632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.14
BayesDel_addAF	Benign	0.0012	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.21
Sift	Benign	0.050	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.52
MutPred		0.26		Gain of sheet (P = 0.0266)
MVP		0.66
MPC		0.43
ClinPred		0.87	D
GERP RS		5.9
Varity_R		0.10
gMVP		0.36
Mutation Taster		=90/10	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

hg19: chr10-86131487;