14-76154488-G-T

Position:

• chr14-76154488-G-T

Variant summary

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

The NM_017926.4(GPATCH2L):​c.125G>T​(p.Arg42Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPATCH2L NM_017926.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.50

Genes affected

GPATCH2L (HGNC:20210): (G-patch domain containing 2 like)

GPATCH2L (HGNC:):

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
GPATCH2L	NM_017926.4	c.125G>T	p.Arg42Leu	missense_variant	2/10	ENST00000261530.12	NP_060396.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPATCH2L	ENST00000261530.12	c.125G>T	p.Arg42Leu	missense_variant	2/10	2	NM_017926.4	ENSP00000261530.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Nov 10, 2024

The c.125G>T (p.R42L) alteration is located in exon 2 (coding exon 1) of the GPATCH2L gene. This alteration results from a G to T substitution at nucleotide position 125, causing the arginine (R) at amino acid position 42 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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T;.;.;T;.;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D;D;.;.;D;D;D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.1	.;.;M;M;M;M;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-7.0	D;D;D;D;D;D;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.016	D;D;D;D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0, 0.99, 1.0	.;.;D;D;D;D;D
Vest4		0.64, 0.67, 0.65, 0.65, 0.67
MutPred		0.29		Loss of methylation at K46 (P = 0.0329);Loss of methylation at K46 (P = 0.0329);Loss of methylation at K46 (P = 0.0329);Loss of methylation at K46 (P = 0.0329);Loss of methylation at K46 (P = 0.0329);Loss of methylation at K46 (P = 0.0329);Loss of methylation at K46 (P = 0.0329);
MVP		0.43
MPC		1.0
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2038202410; hg19: chr14-76620831;