Genetic Variant SPRY2:c.*107G>T (chr13-80336651-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005842.4(SPRY2):c.*107G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,189,010 control chromosomes in the GnomAD database, including 290,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31959 hom., cov: 32)

Exomes 𝑓: 0.70 ( 258436 hom. )

Consequence

SPRY2
NM_005842.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

SPRY2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 13-80336651-C-A is Benign according to our data. Variant chr13-80336651-C-A is described in ClinVar as [Benign]. Clinvar id is 1259792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SPRY2	NM_005842.4 link	c.*107G>T	3_prime_UTR_variant	Exon 2 of 2	ENST00000377104.4	NP_005833.1	O43597
SPRY2	NM_001318536.1 link	c.*107G>T	3_prime_UTR_variant	Exon 2 of 2		NP_001305465.1	O43597
SPRY2	NM_001318537.1 link	c.*107G>T	3_prime_UTR_variant	Exon 2 of 2		NP_001305466.1	O43597
SPRY2	NM_001318538.1 link	c.*107G>T	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
SPRY2	ENST00000377104 link	c.*107G>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_005842.4	ENSP00000366308.3		O43597
SPRY2	ENST00000377102 link	c.*107G>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000366306.1		O43597

Frequencies

GnomAD3 genomes

AF:

0.637

AC:

96737

AN:

151852

Hom.:

31926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.722

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.556

Gnomad FIN

AF:

0.742

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.715

Gnomad OTH

AF:

0.656

GnomAD3 exomes

AF:

0.686

AC:

98206

AN:

143192

Hom.:

34231

AF XY:

0.679

AC XY:

52314

AN XY:

77016

show subpopulations

Gnomad AFR exome

AF:

0.440

Gnomad AMR exome

AF:

0.738

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.756

Gnomad SAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.750

Gnomad NFE exome

AF:

0.715

Gnomad OTH exome

AF:

0.691

GnomAD4 exome

AF:

0.703

AC:

728798

AN:

1037040

Hom.:

258436

Cov.:

AF XY:

0.699

AC XY:

367937

AN XY:

526524

show subpopulations

Gnomad4 AFR exome

AF:

0.442

Gnomad4 AMR exome

AF:

0.734

Gnomad4 ASJ exome

AF:

0.667

Gnomad4 EAS exome

AF:

0.745

Gnomad4 SAS exome

AF:

0.575

Gnomad4 FIN exome

AF:

0.745

Gnomad4 NFE exome

AF:

0.720

Gnomad4 OTH exome

AF:

0.688

GnomAD4 genome

AF:

0.637

AC:

96829

AN:

151970

Hom.:

31959

Cov.:

AF XY:

0.638

AC XY:

47403

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.452

Gnomad4 AMR

AF:

0.695

Gnomad4 ASJ

AF:

0.672

Gnomad4 EAS

AF:

0.744

Gnomad4 SAS

AF:

0.557

Gnomad4 FIN

AF:

0.742

Gnomad4 NFE

AF:

0.715

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.693

Hom.:

49468

Bravo

AF:

0.631

Asia WGS

AF:

0.614

AC:

2135

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 26, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.92

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over