Variant 14-21523209-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001364564.1(SALL2):c.2513C>G(p.Pro838Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,614,038 control chromosomes in the GnomAD database, including 57 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 0.011 ( 32 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 25 hom. )

Consequence

SALL2
NM_001364564.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.90

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027309954).

BP6

Variant 14-21523209-G-C is Benign according to our data. Variant chr14-21523209-G-C is described in ClinVar as [Benign]. Clinvar id is 784278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1660/152216) while in subpopulation AFR AF= 0.0376 (1562/41520). AF 95% confidence interval is 0.0361. There are 32 homozygotes in gnomad4. There are 796 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL2	NM_001364564.1 linkuse as main transcript	c.2513C>G	p.Pro838Arg	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 linkuse as main transcript	c.2513C>G	p.Pro838Arg	missense_variant	2/2	2	NM_001364564.1	ENSP00000438493	P3

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1661

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00767

GnomAD3 exomes

AF:

0.00277

AC:

697

AN:

251382

Hom.:

AF XY:

0.00217

AC XY:

295

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0377

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00110

AC:

1602

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

669

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0377

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.00285

GnomAD4 genome

AF:

0.0109

AC:

1660

AN:

152216

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

796

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0376

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.0128

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0340

AC:

150

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00358

AC:

435

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

SALL2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2024

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

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.74

.;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.39

.;N

REVEL

Benign

0.018

Sift

Uncertain

0.015

.;D

Sift4G

Benign

0.41

T;T

Polyphen

0.063

.;B

Vest4

0.27

MVP

0.46

ClinPred

0.027

GERP RS

2.4

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