14-104706916-T-G

Position:

• chr14-104706916-T-G

Variant summary

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

The NM_022489.4(INF2):​c.850T>G​(p.Cys284Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: INF2 NM_022489.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

INF2 (HGNC:23791): (inverted formin 2) This gene represents a member of the formin family of proteins. It is considered a diaphanous formin due to the presence of a diaphanous inhibitory domain located at the N-terminus of the encoded protein. Studies of a similar mouse protein indicate that the protein encoded by this locus may function in polymerization and depolymerization of actin filaments. Mutations at this locus have been associated with focal segmental glomerulosclerosis 5.[provided by RefSeq, Aug 2010]

INF2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INF2	NM_022489.4	c.850T>G	p.Cys284Gly	missense_variant	7/23	ENST00000392634.9	NP_071934.3
INF2	NM_001031714.4	c.850T>G	p.Cys284Gly	missense_variant	7/22		NP_001026884.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9	c.850T>G	p.Cys284Gly	missense_variant	7/23	5	NM_022489.4	ENSP00000376410.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.21	.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.84	T;T
M_CAP	Pathogenic	0.76	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.95	L;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.41
Sift	Benign	0.61	T;T
Sift4G	Benign	0.62	T;T
Polyphen		0.87	P;P
Vest4		0.35
MutPred		0.59		Gain of catalytic residue at C284 (P = 0.001);Gain of catalytic residue at C284 (P = 0.001);
MVP		0.62
MPC		0.88
ClinPred		0.50	T
GERP RS		-2.6
Varity_R		0.29
gMVP		0.63

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

Other links and lift over

dbSNP: rs374935145; hg19: chr14-105173253;