NM_001321439.2:c.724G>A

Variant names:

• chr19-10923605-C-T
• rs372686960
• NM_001321439.2:c.724G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 13/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• Publications: 5 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08607641).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.724G>A	p.Gly242Arg	missense	Exon 8 of 10	NP_001308368.1	Q9BWQ6
	YIPF2	NM_024029.5		c.724G>A	p.Gly242Arg	missense	Exon 8 of 10	NP_076934.1	Q9BWQ6
	YIPF2	NM_001321440.2		c.607G>A	p.Gly203Arg	missense	Exon 7 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.724G>A	p.Gly242Arg	missense	Exon 8 of 10	ENSP00000466055.1	Q9BWQ6
	YIPF2	ENST00000253031.6	TSL:1	c.724G>A	p.Gly242Arg	missense	Exon 8 of 10	ENSP00000253031.1	Q9BWQ6
	YIPF2	ENST00000874113.1		c.724G>A	p.Gly242Arg	missense	Exon 8 of 10	ENSP00000544172.1

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152174 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000391 AC: 97 AN: 248232 AF XY: 0.000490

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 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.: 2 Cov.: 31 AF XY: 0.000337 AC XY: 245 AN XY: 726690

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.000224 AC: 10 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.000460 AC: 12 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000870 AC: 75 AN: 86236

European-Finnish (FIN) AF: 0.0000948 AC: 5 AN: 52726

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5764

European-Non Finnish (NFE) AF: 0.000261 AC: 290 AN: 1111692

Other (OTH) AF: 0.000481 AC: 29 AN: 60352

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152292 Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74460

African (AFR) AF: 0.0000722 AC: 3 AN: 41554

American (AMR) AF: 0.000196 AC: 3 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000535 Hom.: 0

Bravo AF: 0.000332

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000420 AC: 51

EpiCase AF: 0.000709

EpiControl AF: 0.000771

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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.26
Sift	Benign	0.047	D
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.33
MutPred		0.77		Gain of methylation at G242 (P = 0.0052)
MVP		0.35
MPC		0.46
ClinPred		0.058	T
GERP RS		-0.19
PromoterAI		0.029	Neutral
Varity_R		0.094
gMVP		0.75
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs372686960; hg19: chr19-11034281; COSMIC: COSV99449730; COSMIC: COSV99449730;