Genetic Variant STRIP2:p.Gly44Ser (chr7-129440022-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_020704.3(STRIP2):c.130G>A(p.Gly44Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STRIP2
NM_020704.3 missense, splice_region

Scores

Splicing: ADA: 0.5097

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.01

Variant links:

Genes affected

STRIP2 (HGNC:22209): (striatin interacting protein 2) Involved in cell migration; cytoskeleton organization; and regulation of cell shape. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

STRIP2 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=0.15500712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRIP2	NM_020704.3 link	c.130G>A	p.Gly44Ser	missense_variant, splice_region_variant	Exon 2 of 21	ENST00000249344.7	NP_065755.1	Q9ULQ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRIP2	ENST00000249344.7 link	c.130G>A	p.Gly44Ser	missense_variant, splice_region_variant	Exon 2 of 21	1	NM_020704.3	ENSP00000249344.2		Q9ULQ0-1
STRIP2	ENST00000435494.2 link	c.130G>A	p.Gly44Ser	missense_variant, splice_region_variant	Exon 2 of 20	1		ENSP00000392393.2		Q9ULQ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251352

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135852

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727154

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.130G>A (p.G44S) alteration is located in exon 2 (coding exon 2) of the STRIP2 gene. This alteration results from a G to A substitution at nucleotide position 130, causing the glycine (G) at amino acid position 44 to be replaced by a serine (S). 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

0.096

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.061

Sift

Benign

0.22

T;T

Sift4G

Benign

0.46

T;T

Polyphen

1.0

D;B

Vest4

0.38

MutPred

0.36

Gain of phosphorylation at G44 (P = 0.0152);Gain of phosphorylation at G44 (P = 0.0152);

MVP

0.38

MPC

0.24

ClinPred

0.73

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.51

dbscSNV1_RF

Benign

0.36

SpliceAI score (max)

0.16

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