14-76180806-G-A

Position:

• chr14-76180806-G-A

Variant summary

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

The NM_017926.4(GPATCH2L):​c.1150G>A​(p.Asp384Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,174 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: 0.0000027 (0 hom.)
• Consequence: GPATCH2L NM_017926.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.60

Genes affected

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

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.1150G>A	p.Asp384Asn	missense_variant	8/10	ENST00000261530.12	NP_060396.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPATCH2L	ENST00000261530.12	c.1150G>A	p.Asp384Asn	missense_variant	8/10	2	NM_017926.4	ENSP00000261530.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251462 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135902

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461174 Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 726966

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

May 14, 2024

The c.1150G>A (p.D384N) alteration is located in exon 8 (coding exon 7) of the GPATCH2L gene. This alteration results from a G to A substitution at nucleotide position 1150, causing the aspartic acid (D) at amino acid position 384 to be replaced by an asparagine (N). 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	0.21
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.034	.;T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.2	N;N;.
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D;D;.
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.84
MVP		0.71
MPC		0.83
ClinPred		0.61	D
GERP RS		5.8
Varity_R		0.082
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs376476893; hg19: chr14-76647149; COSMIC: COSV99833952; COSMIC: COSV99833952;