Variant chr14-21523010-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001364564.1(SALL2):c.2712G>C(p.Glu904Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00981 in 1,614,116 control chromosomes in the GnomAD database, including 1,245 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.051 ( 623 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 622 hom. )

Consequence

SALL2
NM_001364564.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.247

Variant links:

Genes affected

SALL2 (HGNC:10526): (spalt like transcription factor 2) This gene encodes a protein containing multiple zinc finger domains. The encoded protein functions in optical fissure closure during development of the eye in the embryo. Mutations in this gene are associated with ocular coloboma. [provided by RefSeq, Jul 2016]

SALL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015507042).

BP6

Variant 14-21523010-C-G is Benign according to our data. Variant chr14-21523010-C-G is described in ClinVar as [Benign]. Clinvar id is 2040752.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL2	NM_001364564.1 link	c.2712G>C	p.Glu904Asp	missense_variant	2/2	ENST00000537235.2	NP_001351493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL2	ENST00000537235.2 link	c.2712G>C	p.Glu904Asp	missense_variant	2/2	2	NM_001364564.1	ENSP00000438493.2		F5H433

Frequencies

GnomAD3 genomes

AF:

0.0509

AC:

7748

AN:

152138

Hom.:

615

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.0351

GnomAD3 exomes

AF:

0.0137

AC:

3447

AN:

251452

Hom.:

265

AF XY:

0.00995

AC XY:

1352

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.181

Gnomad AMR exome

AF:

0.00888

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000730

Gnomad OTH exome

AF:

0.00847

GnomAD4 exome

AF:

0.00550

AC:

8044

AN:

1461860

Hom.:

622

Cov.:

AF XY:

0.00482

AC XY:

3505

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.00451

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000343

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

AF:

0.0512

AC:

7789

AN:

152256

Hom.:

623

Cov.:

AF XY:

0.0497

AC XY:

3702

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.0347

Alfa

AF:

0.00626

Hom.:

Bravo

AF:

0.0580

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.166

AC:

732

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.0169

AC:

2046

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

SALL2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.5

DANN

Benign

0.91

DEOGEN2

Benign

0.021

.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.61

.;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.033

Sift

Benign

0.29

.;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0

.;B

Vest4

0.028

MutPred

0.25

Loss of glycosylation at P904 (P = 0.102);.;

ClinPred

0.0045

GERP RS

-0.41

gMVP

0.13

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