chr14-104714800-G-C

Position:

• chr14-104714800-G-C

Variant summary

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

The NM_022489.4(INF2):​c.3638G>C​(p.Arg1213Pro) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: INF2 NM_022489.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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]

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=0.2081115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INF2	NM_022489.4	c.3638G>C	p.Arg1213Pro	missense_variant	21/23	ENST00000392634.9	NP_071934.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9	c.3638G>C	p.Arg1213Pro	missense_variant	21/23	5	NM_022489.4	ENSP00000376410.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.070	.;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.6	L;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.7	D;D;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.031	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.18
MutPred		0.34		Loss of methylation at R1213 (P = 0.002);Loss of methylation at R1213 (P = 0.002);.;
MVP		0.39
MPC		0.35
ClinPred		0.66	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.10

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: rs199801767; hg19: chr14-105181137;