13-80337279-C-T

Variant names:

• chr13-80337279-C-T
• rs778275764
• NM_005842.4:c.427G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_005842.4(SPRY2):​c.427G>A​(p.Gly143Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SPRY2 NM_005842.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32166287).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRY2	NM_005842.4	c.427G>A	p.Gly143Arg	missense_variant	Exon 2 of 2	ENST00000377104.4	NP_005833.1
SPRY2	NM_001318536.1	c.427G>A	p.Gly143Arg	missense_variant	Exon 2 of 2		NP_001305465.1
SPRY2	NM_001318537.1	c.427G>A	p.Gly143Arg	missense_variant	Exon 2 of 2		NP_001305466.1
SPRY2	NM_001318538.1	c.427G>A	p.Gly143Arg	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.427G>A	p.Gly143Arg	missense_variant	Exon 2 of 2	1	NM_005842.4	ENSP00000366308.3
SPRY2	ENST00000377102.5	c.427G>A	p.Gly143Arg	missense_variant	Exon 2 of 2	1		ENSP00000366306.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251096 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135658

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461382 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726854

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: 0.00000540

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.048
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.83	L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.0	N;N
REVEL	Benign	0.25
Sift	Benign	0.79	T;T
Sift4G	Benign	0.66	T;T
Polyphen		1.0	D;D
Vest4		0.32
MutPred		0.31		Gain of MoRF binding (P = 0.0124);Gain of MoRF binding (P = 0.0124);
MVP		0.83
MPC		1.5
ClinPred		0.37	T
GERP RS		4.2
Varity_R		0.070
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs778275764; hg19: chr13-80911414;