Genetic Variant GAS2L1:p.Arg149Cys (chr22-29308550-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001362985.3(GAS2L1):c.445C>T(p.Arg149Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 1,447,002 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R149S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

GAS2L1
NM_001362985.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

Publications

0 publications found

Variant links:

Genes affected

GAS2L1 (HGNC:16955): (growth arrest specific 2 like 1) This gene encodes a member of the growth arrest-specific 2 protein family. This protein binds components of the cytoskeleton and may be involved in mediating interactions between microtubules and microfilaments. This protein localizes to the proximal end of mature centrioles and links centrosomes to both microtubules and actin. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 9. [provided by RefSeq, May 2018]

GAS2L1 links:

ENSG00000301612 (HGNC:):

ENSG00000301612 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS2L1	NM_001362985.3 link	c.445C>T	p.Arg149Cys	missense_variant	Exon 2 of 6	ENST00000616432.5	NP_001349914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS2L1	ENST00000616432.5 link	c.445C>T	p.Arg149Cys	missense_variant	Exon 2 of 6	1	NM_001362985.3	ENSP00000478908.1		A0A5E8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000263

AC:

AN:

228088

AF XY:

0.0000241

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000388

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.00000898

AC:

AN:

1447002

Hom.:

Cov.:

AF XY:

0.00000835

AC XY:

AN XY:

718676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33224

American (AMR)

AF:

0.0000230

AC:

AN:

43534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25892

East Asian (EAS)

AF:

0.00

AC:

AN:

39304

South Asian (SAS)

AF:

0.00

AC:

AN:

85428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000995

AC:

AN:

1105574

Other (OTH)

AF:

0.0000167

AC:

AN:

59740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.548

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 13, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.445C>T (p.R149C) alteration is located in exon 2 (coding exon 1) of the GAS2L1 gene. This alteration results from a C to T substitution at nucleotide position 445, causing the arginine (R) at amino acid position 149 to be replaced by a cysteine (C). 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

0.22

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.;.;T;T;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.96

.;D;D;.;.;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.52

D;D;D;D;D;D

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.9

.;M;M;.;.;.

PhyloP100

2.2

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-6.1

.;D;.;.;.;.

REVEL

Benign

0.28

Sift

Pathogenic

0.0

.;D;.;.;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;D;D

Vest4

0.52

MutPred

0.66

Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);

MVP

0.54

ClinPred

0.72

GERP RS

2.6

gMVP

0.50

Mutation Taster

=64/36

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

22-29308550-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over