Variant 14-21522208-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000611430.4(SALL2):c.422A>C(p.His141Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,597,170 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 13 hom. )

Consequence

SALL2
ENST00000611430.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.692

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075237453).

BP6

Variant 14-21522208-T-G is Benign according to our data. Variant chr14-21522208-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3033477.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL2	NM_001364564.1 linkuse as main transcript	c.*496A>C		3_prime_UTR_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.*496A>C		3_prime_UTR_variant	2/2	2	NM_001364564.1	ENSP00000438493	P3
	ENST00000535893.1 linkuse as main transcript	n.218-198T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

323

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00362

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00234

AC:

535

AN:

228970

Hom.:

AF XY:

0.00240

AC XY:

303

AN XY:

126318

show subpopulations

Gnomad AFR exome

AF:

0.000804

Gnomad AMR exome

AF:

0.000883

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000538

Gnomad FIN exome

AF:

0.00236

Gnomad NFE exome

AF:

0.00409

Gnomad OTH exome

AF:

0.00223

GnomAD4 exome

AF:

0.00346

AC:

5000

AN:

1444922

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

2402

AN XY:

719004

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.000876

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000454

Gnomad4 FIN exome

AF:

0.00221

Gnomad4 NFE exome

AF:

0.00414

Gnomad4 OTH exome

AF:

0.00347

GnomAD4 genome

AF:

0.00212

AC:

323

AN:

152248

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00362

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00192

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000571

AC:

ESP6500EA

AF:

0.00402

AC:

ExAC

AF:

0.00266

AC:

305

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SALL2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 06, 2020

This variant is classified as likely 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

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0095

.;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.86

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.0075

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

D;N;N;N

Sift4G

Pathogenic

0.0

D;D

Vest4

0.34

MVP

0.30

ClinPred

0.0052

GERP RS

-0.51

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