rs550232203

Variant names:

• chr1-217431188-C-T
• rs550232203
• NM_018040.5:c.1544G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018040.5(GPATCH2):​c.1544G>A​(p.Ser515Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,605,886 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (3 hom.)
• Consequence: GPATCH2 NM_018040.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0640
• Publications: 0 publications found

Genes affected

GPATCH2 (HGNC:25499): (G-patch domain containing 2) The gene encodes a nuclear factor that may play a role in spermatogenesis and in tumor growth during breast cancer. The encoded protein contains a G-patch domain with an RNA binding motif. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046037138).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018040.5. 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
	GPATCH2	NM_018040.5	MANE Select	c.1544G>A	p.Ser515Asn	missense	Exon 10 of 10	NP_060510.1	Q9NW75-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH2	ENST00000366935.8	TSL:2 MANE Select	c.1544G>A	p.Ser515Asn	missense	Exon 10 of 10	ENSP00000355902.3	Q9NW75-1
	GPATCH2	ENST00000885578.1		c.1535G>A	p.Ser512Asn	missense	Exon 10 of 10	ENSP00000555637.1
	GPATCH2	ENST00000911527.1		c.1433G>A	p.Ser478Asn	missense	Exon 8 of 8	ENSP00000581586.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152178 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000306 AC: 77 AN: 251428 AF XY: 0.000412

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000160 AC: 232 AN: 1453594 Hom.: 3 Cov.: 27 AF XY: 0.000211 AC XY: 153 AN XY: 723666

African (AFR) AF: 0.00 AC: 0 AN: 33302

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.00214 AC: 184 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00261 AC: 15 AN: 5754

European-Non Finnish (NFE) AF: 0.0000199 AC: 22 AN: 1104462

Other (OTH) AF: 0.000166 AC: 10 AN: 60124

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152292 Hom.: 1 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41554

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68032

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

Alfa AF: 0.000347 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.000305 AC: 37

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.066
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.064
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.048
Sift	Benign	0.054	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.14		Loss of glycosylation at S515 (P = 0.0102)
MVP		0.17
MPC		0.34
ClinPred		0.018	T
GERP RS		-0.11
Varity_R		0.060
gMVP		0.16
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs550232203; hg19: chr1-217604530; COSMIC: COSV107453766;