Variant 10-68383905-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330103.2(RUFY2):c.832G>A(p.Val278Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RUFY2
NM_001330103.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Variant links:

Genes affected

RUFY2 (HGNC:19761): (RUN and FYVE domain containing 2) Enables SH3 domain binding activity. Predicted to be involved in regulation of endocytosis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RUFY2 links:

RUFY2 (HGNC:):

RUFY2 links:

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ACMG classification

Classification made for transcript

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=0.1294859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY2	NM_001330103.2 linkuse as main transcript	c.832G>A	p.Val278Ile	missense_variant	10/18	ENST00000602465.6	NP_001317032.1	Q8WXA3-2Q5GIA6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUFY2	ENST00000602465.6 linkuse as main transcript	c.832G>A	p.Val278Ile	missense_variant	10/18	5	NM_001330103.2	ENSP00000473462.1		Q8WXA3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249032

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.937G>A (p.V313I) alteration is located in exon 10 (coding exon 10) of the RUFY2 gene. This alteration results from a G to A substitution at nucleotide position 937, causing the valine (V) at amino acid position 313 to be replaced by an isoleucine (I). 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

0.077

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.073

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.87

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.55

N;.;N;N

REVEL

Benign

0.045

Sift

Benign

0.19

T;.;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.21

MutPred

0.19

Loss of disorder (P = 0.1867);.;.;.;

MVP

0.33

MPC

0.35

ClinPred

0.20

GERP RS

4.2

Varity_R

0.022

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over