chr10-84371078-C-G

Position:

• chr10-84371078-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001284240.2(CCSER2):​c.26C>G​(p.Thr9Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 4.14

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24535152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCSER2	NM_001284240.2	c.26C>G	p.Thr9Arg	missense_variant	2/10	ENST00000372088.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCSER2	ENST00000372088.8	c.26C>G	p.Thr9Arg	missense_variant	2/10	2	NM_001284240.2	P4
CCSER2	ENST00000359979.8	c.26C>G	p.Thr9Arg	missense_variant	2/3	1
CCSER2	ENST00000224756.12	c.26C>G	p.Thr9Arg	missense_variant	2/11	5		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Aug 13, 2021

The c.26C>G (p.T9R) alteration is located in exon 2 (coding exon 1) of the CCSER2 gene. This alteration results from a C to G substitution at nucleotide position 26, causing the threonine (T) at amino acid position 9 to be replaced by an arginine (R). 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	0.20
BayesDel_addAF	Benign	-0.0091	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	.;.;T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.4	N;D;N
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.96	D;D;P
Vest4		0.43
MutPred		0.33		Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);
MVP		0.67
MPC		0.22
ClinPred		0.92	D
GERP RS		6.1
Varity_R		0.13
gMVP		0.29

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

Other links and lift over

dbSNP: rs1846036221; hg19: chr10-86130834;