Variant 10-84371301-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001284240.2(CCSER2):c.249C>G(p.Asn83Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CCSER2
NM_001284240.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.599

Variant links:

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]

CCSER2 links:

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ACMG classification

Classification made for transcript

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=0.073981404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCSER2	NM_001284240.2 link	c.249C>G	p.Asn83Lys	missense_variant	2/10	ENST00000372088.8	NP_001271169.1	Q9H7U1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCSER2	ENST00000372088.8 link	c.249C>G	p.Asn83Lys	missense_variant	2/10	2	NM_001284240.2	ENSP00000361160.2	Q9H7U1-3
CCSER2	ENST00000359979.8 link	c.249C>G	p.Asn83Lys	missense_variant	2/3	1		ENSP00000353068.4	Q9H7U1-2
CCSER2	ENST00000224756.12 link	c.249C>G	p.Asn83Lys	missense_variant	2/11	5		ENSP00000224756.8	Q9H7U1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250222

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461312

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2024

The c.249C>G (p.N83K) 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 249, causing the asparagine (N) at amino acid position 83 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.0

DANN

Benign

0.85

DEOGEN2

Benign

0.051

.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.074

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.5

D;N;N

REVEL

Benign

0.015

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0010

B;P;B

Vest4

0.25

MutPred

0.49

Gain of ubiquitination at N83 (P = 0.0051);Gain of ubiquitination at N83 (P = 0.0051);Gain of ubiquitination at N83 (P = 0.0051);

MVP

0.34

MPC

0.13

ClinPred

0.62

GERP RS

-3.4

Varity_R

0.065

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over