rs4334435

Positions:

• chr2-138747565-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007226.3(NXPH2):​c.51+32626A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 152,238 control chromosomes in the GnomAD database, including 67,563 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.94 (67563 hom., cov: 32)
• Consequence: NXPH2 NM_007226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXPH2	NM_007226.3	c.51+32626A>G		intron_variant		ENST00000272641.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXPH2	ENST00000272641.4	c.51+32626A>G		intron_variant		1	NM_007226.3	P1

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142678 AN: 152120 Hom.: 67526 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.987

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.949

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.938 AC: 142768 AN: 152238 Hom.: 67563 Cov.: 32 AF XY: 0.939 AC XY: 69882 AN XY: 74418

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.987

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.949

Alfa AF: 0.985 Hom.: 64512

Bravo AF: 0.929

Asia WGS AF: 0.947 AC: 3292 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.047
DANN	Benign	0.58

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: rs4334435; hg19: chr2-139505135;