14-76173612-G-A

Position:

• chr14-76173612-G-A

Variant summary

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

The NM_017926.4(GPATCH2L):​c.971G>A​(p.Arg324Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GPATCH2L NM_017926.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.40

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.971G>A	p.Arg324Lys	missense_variant	5/10	ENST00000261530.12	NP_060396.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPATCH2L	ENST00000261530.12	c.971G>A	p.Arg324Lys	missense_variant	5/10	2	NM_017926.4	ENSP00000261530.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

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

Mar 19, 2024

The c.971G>A (p.R324K) alteration is located in exon 5 (coding exon 4) of the GPATCH2L gene. This alteration results from a G to A substitution at nucleotide position 971, causing the arginine (R) at amino acid position 324 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	0.19
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	.;.;T;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	.;.;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.57	D;D;D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.8	L;L;L;L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.0	N;N;N;N;.
REVEL	Benign	0.15
Sift	Uncertain	0.021	D;T;T;D;.
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.57	P;P;P;P;P
Vest4		0.67
MutPred		0.30		Gain of catalytic residue at R322 (P = 0.0394);Gain of catalytic residue at R322 (P = 0.0394);Gain of catalytic residue at R322 (P = 0.0394);Gain of catalytic residue at R322 (P = 0.0394);Gain of catalytic residue at R322 (P = 0.0394);
MVP		0.83
MPC		0.48
ClinPred		0.73	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs974043625; hg19: chr14-76639955;