14-76201846-A-G

Position:

• chr14-76201846-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017926.4(GPATCH2L):​c.1444A>G​(p.Ser482Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPATCH2L NM_017926.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.333

Genes affected

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

GPATCH2L (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056869864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPATCH2L	NM_017926.4	c.1444A>G	p.Ser482Gly	missense_variant	10/10	ENST00000261530.12	NP_060396.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPATCH2L	ENST00000261530.12	c.1444A>G	p.Ser482Gly	missense_variant	10/10	2	NM_017926.4	ENSP00000261530.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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, 2022

The c.1444A>G (p.S482G) alteration is located in exon 10 (coding exon 9) of the GPATCH2L gene. This alteration results from a A to G substitution at nucleotide position 1444, causing the serine (S) at amino acid position 482 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	.;T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.70	N;N;.
REVEL	Benign	0.073
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.0	B;B;B
Vest4		0.14
MutPred		0.35		.;Gain of catalytic residue at Y481 (P = 1e-04);.;
MVP		0.24
MPC		0.88
ClinPred		0.45	T
GERP RS		-0.80
Varity_R		0.19
gMVP		0.13

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: rs917942083; hg19: chr14-76668189;