rs11911

Variant names:

• chr13-80336716-A-C
• rs11911
• NM_005842.4:c.*42T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-80336716-A-C
• chr13-80336716-A-G
• chr13-80336716-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005842.4(SPRY2):​c.*42T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,571,972 control chromosomes in the GnomAD database, including 118,873 homozygotes. 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 0.31 (8881 hom., cov: 33)
  • Exomes 𝑓: 0.39 (109992 hom.)
• Consequence: SPRY2 NM_005842.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 19 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.034).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRY2	NM_005842.4	MANE Select	c.*42T>G		3_prime_UTR	Exon 2 of 2	NP_005833.1
	SPRY2	NM_001318536.1		c.*42T>G		3_prime_UTR	Exon 2 of 2	NP_001305465.1
	SPRY2	NM_001318537.1		c.*42T>G		3_prime_UTR	Exon 2 of 2	NP_001305466.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRY2	ENST00000377104.4	TSL:1 MANE Select	c.*42T>G		3_prime_UTR	Exon 2 of 2	ENSP00000366308.3
	SPRY2	ENST00000377102.5	TSL:1	c.*42T>G		3_prime_UTR	Exon 2 of 2	ENSP00000366306.1
	SPRY2	ENST00000909616.1		c.*42T>G		3_prime_UTR	Exon 2 of 2	ENSP00000579675.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47051 AN: 151974 Hom.: 8870 Cov.: 33

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.394 AC: 82860 AN: 210360 AF XY: 0.392

Gnomad AFR exome AF: 0.0703

Gnomad AMR exome AF: 0.525

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.473

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.389 AC: 551943 AN: 1419882 Hom.: 109992 Cov.: 26 AF XY: 0.388 AC XY: 273979 AN XY: 705246

African (AFR) AF: 0.0615 AC: 1999 AN: 32488

American (AMR) AF: 0.516 AC: 20830 AN: 40364

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 8854 AN: 25562

East Asian (EAS) AF: 0.427 AC: 16527 AN: 38716

South Asian (SAS) AF: 0.375 AC: 31040 AN: 82756

European-Finnish (FIN) AF: 0.395 AC: 20520 AN: 51892

Middle Eastern (MID) AF: 0.355 AC: 2028 AN: 5712

European-Non Finnish (NFE) AF: 0.395 AC: 427702 AN: 1083452

Other (OTH) AF: 0.381 AC: 22443 AN: 58940

GnomAD4 genome AF: 0.310 AC: 47072 AN: 152090 Hom.: 8881 Cov.: 33 AF XY: 0.314 AC XY: 23320 AN XY: 74316

African (AFR) AF: 0.0753 AC: 3126 AN: 41538

American (AMR) AF: 0.434 AC: 6638 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2344 AN: 5150

South Asian (SAS) AF: 0.359 AC: 1729 AN: 4818

European-Finnish (FIN) AF: 0.404 AC: 4264 AN: 10552

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26521 AN: 67968

Other (OTH) AF: 0.341 AC: 720 AN: 2112

Alfa AF: 0.373 Hom.: 14267

Bravo AF: 0.304

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.1
DANN	Benign	0.64
PhyloP100		0.16
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: rs11911; hg19: chr13-80910851; COSMIC: COSV65701346;