1-217620173-G-A

Position:

• chr1-217620173-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018040.5(GPATCH2):​c.383C>T​(p.Pro128Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: GPATCH2 NM_018040.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21713978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPATCH2	NM_018040.5	c.383C>T	p.Pro128Leu	missense_variant	2/10	ENST00000366935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPATCH2	ENST00000366935.8	c.383C>T	p.Pro128Leu	missense_variant	2/10	2	NM_018040.5	P1
GPATCH2	ENST00000366934.3	c.383C>T	p.Pro128Leu	missense_variant	2/6	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461624 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2022

The c.383C>T (p.P128L) alteration is located in exon 2 (coding exon 2) of the GPATCH2 gene. This alteration results from a C to T substitution at nucleotide position 383, causing the proline (P) at amino acid position 128 to be replaced by a leucine (L). 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	Benign	0.12
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.24
DEOGEN2	Benign	0.087	T;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Benign	0.14
Sift	Benign	0.37	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.42	B;P
Vest4		0.50
MutPred		0.36		Loss of glycosylation at P128 (P = 0.0167);Loss of glycosylation at P128 (P = 0.0167);
MVP		0.39
MPC		0.45
ClinPred		0.76	D
GERP RS		5.7
Varity_R		0.26
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs1251710925; hg19: chr1-217793515;