Genetic Variant GAS2L2:p.Asn747Ser (chr17-35745257-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_139285.4(GAS2L2):c.2240A>G(p.Asn747Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000473 in 1,608,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

GAS2L2
NM_139285.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.157

Variant links:

Genes affected

GAS2L2 (HGNC:24846): (growth arrest specific 2 like 2) The protein encoded by this gene appears to crosslink microtubules and microfilaments and may be part of the cytoskeleton. This gene is mainly expressed in skeletal muscle. [provided by RefSeq, Jul 2011]

GAS2L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014525384).

BP6

Variant 17-35745257-T-C is Benign according to our data. Variant chr17-35745257-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2541228.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS2L2	NM_139285.4 link	c.2240A>G	p.Asn747Ser	missense_variant	Exon 6 of 6	ENST00000604641.6	NP_644814.1	Q8NHY3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS2L2	ENST00000604641.6 link	c.2240A>G	p.Asn747Ser	missense_variant	Exon 6 of 6	1	NM_139285.4	ENSP00000474529.2		Q8NHY3-1

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000443

AC:

AN:

248348

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

134082

show subpopulations

Gnomad AFR exome

AF:

0.000679

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1456298

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

723628

show subpopulations

Gnomad4 AFR exome

AF:

0.000719

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.000302

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 02, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.57

DANN

Benign

0.55

DEOGEN2

Benign

0.0012

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.81

L;.

PrimateAI

Benign

0.28

Sift4G

Benign

0.93

T;T

Polyphen

0.0010

B;.

Vest4

0.040

MVP

0.18

ClinPred

0.013

GERP RS

-0.54

Varity_R

0.033

gMVP

0.049

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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