NM_018040.5:c.607G>A

Variant names:

• chr1-217619949-C-T
• rs1355966982
• NM_018040.5:c.607G>A

Variant summary

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

The NM_018040.5(GPATCH2):​c.607G>A​(p.Glu203Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPATCH2 NM_018040.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.32
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.607G>A	p.Glu203Lys	missense	Exon 2 of 10	NP_060510.1	Q9NW75-1
	GPATCH2	NM_001297754.3		c.607G>A	p.Glu203Lys	missense	Exon 2 of 6	NP_001284683.1	Q9NW75-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH2	ENST00000366935.8	TSL:2 MANE Select	c.607G>A	p.Glu203Lys	missense	Exon 2 of 10	ENSP00000355902.3	Q9NW75-1
	GPATCH2	ENST00000366934.3	TSL:1	c.607G>A	p.Glu203Lys	missense	Exon 2 of 6	ENSP00000355901.3	Q9NW75-2
	GPATCH2	ENST00000885578.1		c.598G>A	p.Glu200Lys	missense	Exon 2 of 10	ENSP00000555637.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461768 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727182

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111936

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

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	0.26
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.11
Sift	Benign	0.052	T
Sift4G	Benign	0.32	T
Polyphen		0.99	D
Vest4		0.72
MutPred		0.29		Gain of methylation at E203 (P = 0.0102)
MVP		0.55
MPC		0.75
ClinPred		0.80	D
GERP RS		5.7
Varity_R		0.19
gMVP		0.069
Mutation Taster		=67/33	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: rs1355966982; hg19: chr1-217793291; COSMIC: COSV100861393;