Genetic Variant CCSER2:p.Pro909Leu (chr10-84513849-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001284240.2(CCSER2):c.2726C>T(p.Pro909Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,536,232 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 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: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 7 hom. )

Consequence

CCSER2
NM_001284240.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.252

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037968159).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSER2	NM_001284240.2 link	c.2726C>T	p.Pro909Leu	missense_variant	Exon 10 of 10	ENST00000372088.8	NP_001271169.1	Q9H7U1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCSER2	ENST00000372088.8 link	c.2726C>T	p.Pro909Leu	missense_variant	Exon 10 of 10	2	NM_001284240.2	ENSP00000361160.2		Q9H7U1-3

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00172

AC:

243

AN:

140948

AF XY:

0.00188

show subpopulations

Gnomad AFR exome

AF:

0.000902

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000928

Gnomad FIN exome

AF:

0.000284

Gnomad NFE exome

AF:

0.00287

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.00218

AC:

3020

AN:

1383968

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

1489

AN XY:

682918

show subpopulations

African (AFR)

AF:

0.000728

AC:

AN:

31596

American (AMR)

AF:

0.00129

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.0000794

AC:

AN:

25182

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35734

South Asian (SAS)

AF:

0.00136

AC:

108

AN:

79236

European-Finnish (FIN)

AF:

0.000560

AC:

AN:

33958

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00248

AC:

2676

AN:

1078918

Other (OTH)

AF:

0.00247

AC:

143

AN:

57950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

184

368

551

735

919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00188

AC:

286

AN:

152264

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41532

American (AMR)

AF:

0.00255

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00104

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00306

AC:

208

AN:

68024

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00169

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00389

AC:

ExAC

AF:

0.00107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.2

(source)

DANN

Benign

0.41

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-0.98

PROVEAN

Benign

-0.38

N;.

REVEL

Benign

0.016

Sift

Benign

0.50

T;.

Sift4G

Benign

0.28

T;.

Polyphen

0.0010

B;.

Vest4

0.15

MVP

0.072

ClinPred

0.0013

GERP RS

-5.3

gMVP

0.14

Mutation Taster

=92/8

polymorphism

(source)

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.

chr10-84513849-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over