rs2806687

Variant names:

• chr9-100243533-T-C
• rs2806687
• NM_014425.5:c.906+854T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014425.5(INVS):​c.906+854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,846 control chromosomes in the GnomAD database, including 22,031 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 0.52 (22031 hom., cov: 31)
• Consequence: INVS NM_014425.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 3 publications found

Genes affected

INVS (HGNC:17870): (inversin) This gene encodes a protein containing multiple ankyrin domains and two IQ calmodulin-binding domains. The encoded protein may function in renal tubular development and function, and in left-right axis determination. This protein interacts with nephrocystin and infers a connection between primary cilia function and left-right axis determination. A similar protein in mice interacts with calmodulin. Mutations in this gene have been associated with nephronophthisis type 2. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2012]

INVS Gene-Disease associations (from GenCC):

• nephronophthisis 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014425.5. 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
	INVS	NM_014425.5	MANE Select	c.906+854T>C		intron	N/A	NP_055240.2
	INVS	NM_001318381.2		c.618+854T>C		intron	N/A	NP_001305310.1
	INVS	NM_001318382.2		c.-84+854T>C		intron	N/A	NP_001305311.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INVS	ENST00000262457.7	TSL:1 MANE Select	c.906+854T>C		intron	N/A	ENSP00000262457.2
	INVS	ENST00000262456.6	TSL:5	c.906+854T>C		intron	N/A	ENSP00000262456.2

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79442 AN: 151728 Hom.: 21987 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.524 AC: 79546 AN: 151846 Hom.: 22031 Cov.: 31 AF XY: 0.515 AC XY: 38192 AN XY: 74202

African (AFR) AF: 0.648 AC: 26840 AN: 41390

American (AMR) AF: 0.400 AC: 6097 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1379 AN: 3466

East Asian (EAS) AF: 0.0963 AC: 497 AN: 5160

South Asian (SAS) AF: 0.274 AC: 1321 AN: 4814

European-Finnish (FIN) AF: 0.522 AC: 5481 AN: 10508

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.531 AC: 36073 AN: 67948

Other (OTH) AF: 0.507 AC: 1065 AN: 2100

Alfa AF: 0.519 Hom.: 3899

Bravo AF: 0.519

Asia WGS AF: 0.250 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.65
PhyloP100		0.21
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: rs2806687; hg19: chr9-103005815;