chr13-80336651-C-A

Variant names:

• chr13-80336651-C-A
• rs4728
• NM_005842.4:c.*107G>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.673
• Publications: 23 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Tourette syndrome

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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.108).
• BP6: Variant 13-80336651-C-A is Benign according to our data. Variant chr13-80336651-C-A is described in ClinVar as Benign. ClinVar VariationId 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.

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.*107G>T		3_prime_UTR	Exon 2 of 2	NP_005833.1	O43597
	SPRY2	NM_001318536.1		c.*107G>T		3_prime_UTR	Exon 2 of 2	NP_001305465.1	O43597
	SPRY2	NM_001318537.1		c.*107G>T		3_prime_UTR	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.*107G>T		3_prime_UTR	Exon 2 of 2	ENSP00000366308.3	O43597
	SPRY2	ENST00000377102.5	TSL:1	c.*107G>T		3_prime_UTR	Exon 2 of 2	ENSP00000366306.1	O43597
	SPRY2	ENST00000909616.1		c.*107G>T		3_prime_UTR	Exon 2 of 2	ENSP00000579675.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96737 AN: 151852 Hom.: 31926 Cov.: 32

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

GnomAD2 exomes AF: 0.686 AC: 98206 AN: 143192 AF XY: 0.679

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 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.: 14 AF XY: 0.699 AC XY: 367937 AN XY: 526524

African (AFR) AF: 0.442 AC: 10662 AN: 24146

American (AMR) AF: 0.734 AC: 25402 AN: 34620

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 15196 AN: 22776

East Asian (EAS) AF: 0.745 AC: 25446 AN: 34144

South Asian (SAS) AF: 0.575 AC: 40698 AN: 70748

European-Finnish (FIN) AF: 0.745 AC: 30073 AN: 40368

Middle Eastern (MID) AF: 0.642 AC: 3235 AN: 5042

European-Non Finnish (NFE) AF: 0.720 AC: 546253 AN: 758922

Other (OTH) AF: 0.688 AC: 31833 AN: 46274

GnomAD4 genome AF: 0.637 AC: 96829 AN: 151970 Hom.: 31959 Cov.: 32 AF XY: 0.638 AC XY: 47403 AN XY: 74260

African (AFR) AF: 0.452 AC: 18728 AN: 41426

American (AMR) AF: 0.695 AC: 10616 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2329 AN: 3468

East Asian (EAS) AF: 0.744 AC: 3843 AN: 5168

South Asian (SAS) AF: 0.557 AC: 2689 AN: 4828

European-Finnish (FIN) AF: 0.742 AC: 7826 AN: 10550

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48560 AN: 67946

Other (OTH) AF: 0.658 AC: 1391 AN: 2114

Alfa AF: 0.686 Hom.: 61577

Bravo AF: 0.631

Asia WGS AF: 0.614 AC: 2135 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

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: rs4728; hg19: chr13-80910786;