10-84371731-T-A

Position:

• chr10-84371731-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCSER2	NM_001284240.2	c.679T>A	p.Ser227Thr	missense_variant	2/10	ENST00000372088.8	NP_001271169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCSER2	ENST00000372088.8	c.679T>A	p.Ser227Thr	missense_variant	2/10	2	NM_001284240.2	ENSP00000361160.2
CCSER2	ENST00000359979.8	c.679T>A	p.Ser227Thr	missense_variant	2/3	1		ENSP00000353068.4
CCSER2	ENST00000224756.12	c.679T>A	p.Ser227Thr	missense_variant	2/11	5		ENSP00000224756.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.679T>A (p.S227T) alteration is located in exon 2 (coding exon 1) of the CCSER2 gene. This alteration results from a T to A substitution at nucleotide position 679, causing the serine (S) at amino acid position 227 to be replaced by a threonine (T). 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	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;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.5	M;M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.050	D;T;T
Sift4G	Benign	0.12	T;D;T
Polyphen		1.0	D;D;D
Vest4		0.52
MutPred		0.26		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-86131487;