Genetic Variant VASP:p.Pro211Gln (chr19-45522493-C-A) – 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_003370.4(VASP):c.632C>A(p.Pro211Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000076 in 1,315,164 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P211L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

VASP
NM_003370.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37

Publications

0 publications found

Variant links:

Genes affected

VASP (HGNC:12652): (vasodilator stimulated phosphoprotein) Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena-VASP protein family. Ena-VASP family members contain an EHV1 N-terminal domain that binds proteins containing E/DFPPPPXD/E motifs and targets Ena-VASP proteins to focal adhesions. In the mid-region of the protein, family members have a proline-rich domain that binds SH3 and WW domain-containing proteins. Their C-terminal EVH2 domain mediates tetramerization and binds both G and F actin. VASP is associated with filamentous actin formation and likely plays a widespread role in cell adhesion and motility. VASP may also be involved in the intracellular signaling pathways that regulate integrin-extracellular matrix interactions. VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG. [provided by RefSeq, Jul 2008]

VASP links:

LOC107985315 (HGNC:):

LOC107985315 links:

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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;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003370.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VASP	NM_003370.4	MANE Select	c.632C>A	p.Pro211Gln	missense	Exon 6 of 13	NP_003361.1	A0A024R0V4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VASP	ENST00000245932.11	TSL:1 MANE Select	c.632C>A	p.Pro211Gln	missense	Exon 6 of 13	ENSP00000245932.5	P50552
VASP	ENST00000916562.1		c.725C>A	p.Pro242Gln	missense	Exon 6 of 13	ENSP00000586621.1
VASP	ENST00000862928.1		c.659C>A	p.Pro220Gln	missense	Exon 6 of 13	ENSP00000532987.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.60e-7

AC:

AN:

1315164

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

641574

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28808

American (AMR)

AF:

0.00

AC:

AN:

22162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19276

East Asian (EAS)

AF:

0.00

AC:

AN:

35392

South Asian (SAS)

AF:

0.00

AC:

AN:

65130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3986

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1045060

Other (OTH)

AF:

0.0000184

AC:

AN:

54356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.88

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.71

M_CAP

Pathogenic

0.30

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

-0.019

MutationAssessor

Pathogenic

3.3

PhyloP100

3.4

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.36

Sift

Benign

0.12

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.55

MutPred

0.13

Loss of loop (P = 0.0128)

MVP

0.68

MPC

0.32

ClinPred

0.98

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.39

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over