9-100292825-G-T

Position:

• chr9-100292825-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014425.5(INVS):​c.2568G>T​(p.Arg856Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R856R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INVS NM_014425.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.834

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1821284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INVS	NM_014425.5	c.2568G>T	p.Arg856Ser	missense_variant	14/17	ENST00000262457.7
INVS	NM_001318381.2	c.2280G>T	p.Arg760Ser	missense_variant	15/18
INVS	NM_001318382.2	c.1590G>T	p.Arg530Ser	missense_variant	14/17
INVS	NR_134606.2	n.2717G>T		non_coding_transcript_exon_variant	14/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INVS	ENST00000262457.7	c.2568G>T	p.Arg856Ser	missense_variant	14/17	1	NM_014425.5	A2
INVS	ENST00000262456.6	c.2180-122G>T		intron_variant		5		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.14
Sift	Benign	0.060	T
Sift4G	Benign	0.38	T
Polyphen		0.68	P
Vest4		0.19
MutPred		0.13		Gain of phosphorylation at R856 (P = 0.0285);
MVP		0.71
MPC		0.44
ClinPred		0.35	T
GERP RS		1.4
Varity_R		0.10
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-103055107; COSMIC: COSV52447121;