13-80336864-C-T

Variant names:

• chr13-80336864-C-T
• rs79066821
• NM_005842.4:c.842G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005842.4(SPRY2):​c.842G>A​(p.Gly281Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000121 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SPRY2 NM_005842.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67
• Publications: 1 publications found

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]

SPRY2 Gene-Disease associations (from GenCC):

• IgA nephropathy, susceptibility to, 3

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005842.4. 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
	SPRY2	NM_005842.4	MANE Select	c.842G>A	p.Gly281Glu	missense	Exon 2 of 2	NP_005833.1	O43597
	SPRY2	NM_001318536.1		c.842G>A	p.Gly281Glu	missense	Exon 2 of 2	NP_001305465.1	O43597
	SPRY2	NM_001318537.1		c.842G>A	p.Gly281Glu	missense	Exon 2 of 2	NP_001305466.1	O43597

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRY2	ENST00000377104.4	TSL:1 MANE Select	c.842G>A	p.Gly281Glu	missense	Exon 2 of 2	ENSP00000366308.3	O43597
	SPRY2	ENST00000377102.5	TSL:1	c.842G>A	p.Gly281Glu	missense	Exon 2 of 2	ENSP00000366306.1	O43597
	SPRY2	ENST00000909616.1		c.842G>A	p.Gly281Glu	missense	Exon 2 of 2	ENSP00000579675.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152058 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251444 AF XY: 0.0000368

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000131 AC: 191 AN: 1461866 Hom.: 0 Cov.: 32 AF XY: 0.000118 AC XY: 86 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1112012

Other (OTH) AF: 0.000298 AC: 18 AN: 60396

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152058 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74244

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	0.0091	T
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Benign	0.93
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.7
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.20
Sift	Benign	0.79	T
Sift4G	Benign	0.97	T
Polyphen		1.0	D
Vest4		0.71
MVP		0.55
MPC		1.5
ClinPred		0.45	T
GERP RS		5.2
Varity_R		0.24
gMVP		0.82
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs79066821; hg19: chr13-80910999;