Variant chr14-21523215-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001364564.1(SALL2):c.2507C>T(p.Pro836Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,614,066 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

SALL2
NM_001364564.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.529

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059536397).

BP6

Variant 14-21523215-G-A is Benign according to our data. Variant chr14-21523215-G-A is described in ClinVar as [Benign]. Clinvar id is 739905.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-21523215-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL2	NM_001364564.1 link	c.2507C>T	p.Pro836Leu	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.2507C>T	p.Pro836Leu	missense_variant	2/2	2	NM_001364564.1	ENSP00000438493.2		F5H433

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

317

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00746

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000509

AC:

128

AN:

251378

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00738

Gnomad AMR exome

AF:

0.000173

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:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000205

AC:

299

AN:

1461788

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

117

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00786

Gnomad4 AMR exome

AF:

0.000224

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:

0.00000270

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.00208

AC:

317

AN:

152278

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00744

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000379

Hom.:

Bravo

AF:

0.00230

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000692

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Jul 12, 2023

- -

SALL2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 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

0.065

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-0.90

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

.;N

REVEL

Benign

0.034

Sift

Uncertain

0.0020

.;D

Sift4G

Benign

0.40

T;T

Polyphen

0.0010

.;B

Vest4

0.24

MVP

0.38

ClinPred

0.027

GERP RS

2.2

gMVP

0.35

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