19-45522412-C-G

Variant names:

• chr19-45522412-C-G
• rs554683036
• NM_003370.4:c.551C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003370.4(VASP):​c.551C>G​(p.Pro184Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,379,616 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: VASP NM_003370.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88

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]

LOC107985315 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 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
VASP	NM_003370.4	c.551C>G	p.Pro184Arg	missense_variant	Exon 6 of 13	ENST00000245932.11	NP_003361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VASP	ENST00000245932.11	c.551C>G	p.Pro184Arg	missense_variant	Exon 6 of 13	1	NM_003370.4	ENSP00000245932.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1379616 Hom.: 0 Cov.: 34 AF XY: 0.00000147 AC XY: 1 AN XY: 679292

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: 9.35e-7

Gnomad4 OTH exome AF: 0.0000175

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Pathogenic	0.84	D
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.42	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.25
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.079	B
Vest4		0.50
MutPred		0.37		Loss of glycosylation at P184 (P = 0.004);
MVP		0.54
MPC		0.36
ClinPred		0.77	D
GERP RS		3.3
Varity_R		0.17
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs554683036; hg19: chr19-46025670;