Variant chr2-102619954-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003048.6(SLC9A2):c.106T>A(p.Leu36Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,762 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 32)

Exomes 𝑓: 0.0000034 ( 1 hom. )

Consequence

SLC9A2
NM_003048.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

Variant links:

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]

SLC9A2 links:

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ACMG classification

Classification made for transcript

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=0.25280744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A2	NM_003048.6 linkuse as main transcript	c.106T>A	p.Leu36Met	missense_variant	1/12	ENST00000233969.3	NP_003039.2	Q9UBY0
SLC9A2	XM_047445572.1 linkuse as main transcript	c.-217T>A		5_prime_UTR_premature_start_codon_gain_variant	1/11		XP_047301528.1
SLC9A2	XM_047445572.1 linkuse as main transcript	c.-217T>A		5_prime_UTR_variant	1/11		XP_047301528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A2	ENST00000233969.3 linkuse as main transcript	c.106T>A	p.Leu36Met	missense_variant	1/12	1	NM_003048.6	ENSP00000233969.2		Q9UBY0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459762

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726054

show subpopulations

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:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.106T>A (p.L36M) alteration is located in exon 1 (coding exon 1) of the SLC9A2 gene. This alteration results from a T to A substitution at nucleotide position 106, causing the leucine (L) at amino acid position 36 to be replaced by a methionine (M). 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

0.095

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.45

M_CAP

Benign

0.076

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.070

REVEL

Benign

0.10

Sift

Benign

0.062

Sift4G

Benign

0.11

Polyphen

0.99

Vest4

0.23

MutPred

0.27

Gain of glycosylation at T35 (P = 0.0865);

MVP

0.66

MPC

0.72

ClinPred

0.29

GERP RS

1.8

Varity_R

0.070

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over