Genetic Variant YIPF2:p.Gly242Arg (chr19-10923605-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001321439.2(YIPF2):c.724G>A(p.Gly242Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,612,992 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

YIPF2
NM_001321439.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

YIPF2 (HGNC:28476): (Yip1 domain family member 2) Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle-mediated transport. Located in Golgi apparatus subcompartment and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

YIPF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08607641).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YIPF2	NM_001321439.2 link	c.724G>A	p.Gly242Arg	missense_variant	Exon 8 of 10	ENST00000586748.6	NP_001308368.1	Q9BWQ6A0A024R7E1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YIPF2	ENST00000586748.6 link	c.724G>A	p.Gly242Arg	missense_variant	Exon 8 of 10	1	NM_001321439.2	ENSP00000466055.1		Q9BWQ6

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000391

AC:

AN:

248232

Hom.:

AF XY:

0.000490

AC XY:

AN XY:

134706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000501

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000981

Gnomad FIN exome

AF:

0.0000480

Gnomad NFE exome

AF:

0.000401

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000296

AC:

432

AN:

1460700

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

245

AN XY:

726690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.000460

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000870

Gnomad4 FIN exome

AF:

0.0000948

Gnomad4 NFE exome

AF:

0.000261

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.000263

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000535

Hom.:

Bravo

AF:

0.000332

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.724G>A (p.G242R) alteration is located in exon 8 (coding exon 7) of the YIPF2 gene. This alteration results from a G to A substitution at nucleotide position 724, causing the glycine (G) at amino acid position 242 to be replaced by an arginine (R). 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;T;.;.;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

.;T;T;D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.086

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

N;N;.;.;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.47

N;.;.;.;.;.

REVEL

Benign

0.26

Sift

Benign

0.047

D;.;.;.;.;.

Sift4G

Benign

0.21

T;T;T;T;.;.

Polyphen

0.99

D;D;.;.;.;.

Vest4

0.33

MutPred

0.77

Gain of methylation at G242 (P = 0.0052);Gain of methylation at G242 (P = 0.0052);.;.;.;.;

MVP

0.35

MPC

0.46

ClinPred

0.058

GERP RS

-0.19

Varity_R

0.094

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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