chr1-217619949-C-T

Position:

• chr1-217619949-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPATCH2	NM_018040.5	c.607G>A	p.Glu203Lys	missense_variant	2/10	ENST00000366935.8	NP_060510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPATCH2	ENST00000366935.8	c.607G>A	p.Glu203Lys	missense_variant	2/10	2	NM_018040.5	ENSP00000355902.3
GPATCH2	ENST00000366934.3	c.607G>A	p.Glu203Lys	missense_variant	2/6	1		ENSP00000355901.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

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 24, 2022

The c.607G>A (p.E203K) alteration is located in exon 2 (coding exon 2) of the GPATCH2 gene. This alteration results from a G to A substitution at nucleotide position 607, causing the glutamic acid (E) at amino acid position 203 to be replaced by a lysine (K). 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	0.26
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;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.83	N;N
REVEL	Benign	0.11
Sift	Benign	0.052	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.99	D;D
Vest4		0.72
MutPred		0.29		Gain of methylation at E203 (P = 0.0102);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-217793291; COSMIC: COSV100861393;