rs17775170

Positions:

• chr2-102635468-G-A
• chr2-102635468-G-C

Variant summary

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

The NM_003048.6(SLC9A2):​c.289+15331G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,142 control chromosomes in the GnomAD database, including 2,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.18 (2931 hom., cov: 33)
• Consequence: SLC9A2 NM_003048.6 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.437

Genes affected

SLC9A2 (HGNC:11072): (solute carrier family 9 member A2) This gene encodes a member of the sodium-hydrogen exchanger (NHE) protein family. These proteins are involved in sodium-ion transport by exchanging intracellular hydrogen ions to external sodium ions and help in the regulation of cell pH and volume. The encoded protein is localized to the apical membrane and is involved in apical absorption of sodium. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A2	NM_003048.6	c.289+15331G>A		intron_variant		ENST00000233969.3	NP_003039.2
SLC9A2	XM_047445572.1	c.-34+15331G>A		intron_variant			XP_047301528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A2	ENST00000233969.3	c.289+15331G>A		intron_variant		1	NM_003048.6	ENSP00000233969.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27079 AN: 152024 Hom.: 2923 Cov.: 33

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.178 AC: 27102 AN: 152142 Hom.: 2931 Cov.: 33 AF XY: 0.179 AC XY: 13330 AN XY: 74386

Gnomad4 AFR AF: 0.0801

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.163

Alfa AF: 0.200 Hom.: 1565

Bravo AF: 0.185

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ascending aortic dissection Other:1

association, no assertion criteria provided

case-control

Beijing Anzhen Hospital, Capital Medical University

Feb 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.57
DANN	Benign	0.66

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: rs17775170; hg19: chr2-103251927;