chr13-80336651-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005842.4(SPRY2):​c.*107G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 9.6e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SPRY2
NM_005842.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.673
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPRY2NM_005842.4 linkc.*107G>A 3_prime_UTR_variant Exon 2 of 2 ENST00000377104.4 NP_005833.1 O43597
SPRY2NM_001318536.1 linkc.*107G>A 3_prime_UTR_variant Exon 2 of 2 NP_001305465.1 O43597
SPRY2NM_001318537.1 linkc.*107G>A 3_prime_UTR_variant Exon 2 of 2 NP_001305466.1 O43597
SPRY2NM_001318538.1 linkc.*107G>A 3_prime_UTR_variant Exon 2 of 2 NP_001305467.1 O43597

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPRY2ENST00000377104 linkc.*107G>A 3_prime_UTR_variant Exon 2 of 2 1 NM_005842.4 ENSP00000366308.3 O43597
SPRY2ENST00000377102 linkc.*107G>A 3_prime_UTR_variant Exon 2 of 2 1 ENSP00000366306.1 O43597

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151902
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000698
AC:
1
AN:
143192
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
77016
show subpopulations
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:
0.00
Gnomad OTH exome
AF:
0.000239
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
9.63e-7
AC:
1
AN:
1038794
Hom.:
0
Cov.:
14
AF XY:
0.00
AC XY:
0
AN XY:
527368
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.0000216
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151902
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74164
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
14
DANN
Benign
0.96

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4728; hg19: chr13-80910786; API