2-197572265-G-A

Position:

• chr2-197572265-G-A

Variant summary

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

The NM_144629.3(RFTN2):​c.1249C>T​(p.His417Tyr) variant causes a missense change. 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RFTN2 NM_144629.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

Genes affected

RFTN2 (HGNC:26402): (raftlin family member 2) Predicted to act upstream of or within dsRNA transport and response to exogenous dsRNA. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC124907952 (HGNC:):

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=0.0709711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFTN2	NM_144629.3	c.1249C>T	p.His417Tyr	missense_variant	9/9	ENST00000295049.9	NP_653230.2
LOC124907952	XR_007087918.1	n.1390G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFTN2	ENST00000295049.9	c.1249C>T	p.His417Tyr	missense_variant	9/9	1	NM_144629.3	ENSP00000295049	P1
RFTN2	ENST00000454447.1	c.325C>T	p.His109Tyr	missense_variant	5/5	3		ENSP00000387459
RFTN2	ENST00000494346.1	n.421C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2024

The c.1249C>T (p.H417Y) alteration is located in exon 9 (coding exon 9) of the RFTN2 gene. This alteration results from a C to T substitution at nucleotide position 1249, causing the histidine (H) at amino acid position 417 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.69
DEOGEN2	Benign	0.0084	T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.68	N;N
REVEL	Benign	0.055
Sift	Benign	0.73	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.34	B;.
Vest4		0.14
MutPred		0.22		Loss of ubiquitination at K412 (P = 0.0401);.;
MVP		0.076
MPC		0.066
ClinPred		0.15	T
GERP RS		2.7
Varity_R		0.046
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr2-198436989;