2-138671527-G-C

Position:

• chr2-138671527-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007226.3(NXPH2):​c.190C>G​(p.Pro64Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NXPH2 NM_007226.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

Genes affected

NXPH2 (HGNC:8076): (neurexophilin 2) Predicted to enable signaling receptor binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12161064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPH2	NM_007226.3	c.190C>G	p.Pro64Ala	missense_variant	2/2	ENST00000272641.4	NP_009157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NXPH2	ENST00000272641.4	c.190C>G	p.Pro64Ala	missense_variant	2/2	1	NM_007226.3	ENSP00000272641.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461686 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727118

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

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

Oct 04, 2024

The c.190C>G (p.P64A) alteration is located in exon 2 (coding exon 2) of the NXPH2 gene. This alteration results from a C to G substitution at nucleotide position 190, causing the proline (P) at amino acid position 64 to be replaced by an alanine (A). 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	0.059
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.064
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.071
Sift	Benign	0.089	T
Sift4G	Benign	0.066	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.49		Loss of disorder (P = 0.06);
MVP		0.068
MPC		0.59
ClinPred		0.55	D
GERP RS		4.4
Varity_R		0.083
gMVP		0.38

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: chr2-139429097;