chr13-80337254-C-A

Variant names:

• chr13-80337254-C-A
• NM_005842.4:c.452G>T

Variant summary

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

The NM_005842.4(SPRY2):​c.452G>T​(p.Arg151Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,052 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPRY2 NM_005842.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64

Genes affected

SPRY2 (HGNC:11270): (sprouty RTK signaling antagonist 2) This gene encodes a protein belonging to the sprouty family. The encoded protein contains a carboxyl-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase signaling proteins and is required for growth factor stimulated translocation of the protein to membrane ruffles. In primary dermal endothelial cells this gene is transiently upregulated in response to fibroblast growth factor two. This protein is indirectly involved in the non-cell autonomous inhibitory effect on fibroblast growth factor two signaling. The protein interacts with Cas-Br-M (murine) ectropic retroviral transforming sequence, and can function as a bimodal regulator of epidermal growth factor receptor/mitogen-activated protein kinase signaling. This protein may play a role in alveoli branching during lung development as shown by a similar mouse protein. [provided by RefSeq, Jul 2008]

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
SPRY2	NM_005842.4	c.452G>T	p.Arg151Leu	missense_variant	Exon 2 of 2	ENST00000377104.4	NP_005833.1
SPRY2	NM_001318536.1	c.452G>T	p.Arg151Leu	missense_variant	Exon 2 of 2		NP_001305465.1
SPRY2	NM_001318537.1	c.452G>T	p.Arg151Leu	missense_variant	Exon 2 of 2		NP_001305466.1
SPRY2	NM_001318538.1	c.452G>T	p.Arg151Leu	missense_variant	Exon 2 of 2		NP_001305467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRY2	ENST00000377104.4	c.452G>T	p.Arg151Leu	missense_variant	Exon 2 of 2	1	NM_005842.4	ENSP00000366308.3
SPRY2	ENST00000377102.5	c.452G>T	p.Arg151Leu	missense_variant	Exon 2 of 2	1		ENSP00000366306.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460052 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725854

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.0096	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.99	D;D
Vest4		0.56
MutPred		0.50		Gain of catalytic residue at A146 (P = 0.0161);Gain of catalytic residue at A146 (P = 0.0161);
MVP		0.40
MPC		0.59
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.50
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-80911389; COSMIC: COSV101001707;