Variant 9-19528071-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020344.4(SLC24A2):c.1547T>G(p.Leu516Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,443,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

SLC24A2
NM_020344.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.10

Variant links:

Genes affected

SLC24A2 (HGNC:10976): (solute carrier family 24 member 2) This gene encodes a member of the calcium/cation antiporter superfamily of transport proteins. The encoded protein belongs to the SLC24 branch of exchangers, which can mediate the extrusion of one Ca2+ ion and one K+ ion in exchange for four Na+ ions. This family member is a retinal cone/brain exchanger that can mediate a light-induced decrease in free Ca2+ concentration. This protein may also play a neuroprotective role during ischemic brain injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

SLC24A2 links:

LOC105375988 (HGNC:):

LOC105375988 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A2	NM_020344.4 linkuse as main transcript	c.1547T>G	p.Leu516Trp	missense_variant	9/11	ENST00000341998.7	NP_065077.1	Q9UI40-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A2	ENST00000341998.7 linkuse as main transcript	c.1547T>G	p.Leu516Trp	missense_variant	9/11	1	NM_020344.4	ENSP00000344801.1		Q9UI40-1
SLC24A2	ENST00000286344.4 linkuse as main transcript	c.1496T>G	p.Leu499Trp	missense_variant	8/10	1		ENSP00000286344.3		Q9UI40-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000133

AC:

AN:

226146

Hom.:

AF XY:

0.00000829

AC XY:

AN XY:

120686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000297

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1443980

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716062

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000453

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

AC:

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

Jan 20, 2023

The c.1547T>G (p.L516W) alteration is located in exon 8 (coding exon 8) of the SLC24A2 gene. This alteration results from a T to G substitution at nucleotide position 1547, causing the leucine (L) at amino acid position 516 to be replaced by a tryptophan (W). 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

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Uncertain

0.68

D;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.86

MVP

0.97

MPC

0.61

ClinPred

0.98

GERP RS

6.2

Varity_R

0.87

gMVP

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over