chr19-10923358-T-C

Variant names:

• chr19-10923358-T-C
• rs2074297308
• NM_001321439.2:c.884A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321439.2(YIPF2):​c.884A>G​(p.Gln295Arg) 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. 16/21 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: YIPF2 NM_001321439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0410
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069377154).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321439.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YIPF2	NM_001321439.2	MANE Select	c.884A>G	p.Gln295Arg	missense	Exon 9 of 10	NP_001308368.1	Q9BWQ6
	YIPF2	NM_024029.5		c.884A>G	p.Gln295Arg	missense	Exon 9 of 10	NP_076934.1	Q9BWQ6
	YIPF2	NM_001321440.2		c.767A>G	p.Gln256Arg	missense	Exon 8 of 9	NP_001308369.1	K7ENM8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YIPF2	ENST00000586748.6	TSL:1 MANE Select	c.884A>G	p.Gln295Arg	missense	Exon 9 of 10	ENSP00000466055.1	Q9BWQ6
	YIPF2	ENST00000253031.6	TSL:1	c.884A>G	p.Gln295Arg	missense	Exon 9 of 10	ENSP00000253031.1	Q9BWQ6
	YIPF2	ENST00000874113.1		c.884A>G	p.Gln295Arg	missense	Exon 9 of 10	ENSP00000544172.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.5
DANN	Benign	0.69
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.041
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.056
Sift	Benign	0.48	T
Sift4G	Benign	0.55	T
Polyphen		0.079	B
Vest4		0.23
MutPred		0.19		Gain of phosphorylation at S298 (P = 0.0613)
MVP		0.055
MPC		0.14
ClinPred		0.044	T
GERP RS		2.3
PromoterAI		0.0089	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.28
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2074297308; hg19: chr19-11034034;