1-217619837-T-G

Variant names:

• chr1-217619837-T-G
• NM_018040.5:c.719A>C

Variant summary

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

The NM_018040.5(GPATCH2):​c.719A>C​(p.Lys240Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPATCH2 NM_018040.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63

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 rank	MANE	Protein	UniProt
GPATCH2	NM_018040.5	c.719A>C	p.Lys240Thr	missense_variant	Exon 2 of 10	ENST00000366935.8	NP_060510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH2	ENST00000366935.8	c.719A>C	p.Lys240Thr	missense_variant	Exon 2 of 10	2	NM_018040.5	ENSP00000355902.3
GPATCH2	ENST00000366934.3	c.719A>C	p.Lys240Thr	missense_variant	Exon 2 of 6	1		ENSP00000355901.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.719A>C (p.K240T) alteration is located in exon 2 (coding exon 2) of the GPATCH2 gene. This alteration results from a A to C substitution at nucleotide position 719, causing the lysine (K) at amino acid position 240 to be replaced by a threonine (T). 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	0.22
BayesDel_addAF	Benign	-0.0034	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Benign	0.27
Sift	Benign	0.099	T;D
Sift4G	Benign	0.13	T;D
Polyphen		1.0	D;D
Vest4		0.60
MutPred		0.23		Loss of ubiquitination at K240 (P = 0.0017);Loss of ubiquitination at K240 (P = 0.0017);
MVP		0.65
MPC		0.88
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.22

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: chr1-217793179; COSMIC: COSV65128378;