Genetic Variant NM_001364564.1:c.2226G>A (chr14-21523496-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001364564.1(SALL2):c.2226G>A(p.Gly742Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 1,614,178 control chromosomes in the GnomAD database, including 663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 42 hom., cov: 33)

Exomes 𝑓: 0.026 ( 621 hom. )

Consequence

SALL2
NM_001364564.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.689

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 14-21523496-C-T is Benign according to our data. Variant chr14-21523496-C-T is described in ClinVar as [Benign]. Clinvar id is 2039674.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.689 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.021 (3197/152314) while in subpopulation SAS AF= 0.0327 (158/4832). AF 95% confidence interval is 0.0285. There are 42 homozygotes in gnomad4. There are 1534 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL2	NM_001364564.1 link	c.2226G>A	p.Gly742Gly	synonymous_variant	Exon 2 of 2	ENST00000537235.2	NP_001351493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL2	ENST00000537235.2 link	c.2226G>A	p.Gly742Gly	synonymous_variant	Exon 2 of 2	2	NM_001364564.1	ENSP00000438493.2		F5H433

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3187

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.0318

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0264

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0236

AC:

5923

AN:

251094

Hom.:

106

AF XY:

0.0245

AC XY:

3323

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.0321

Gnomad ASJ exome

AF:

0.0205

Gnomad EAS exome

AF:

0.00228

Gnomad SAS exome

AF:

0.0352

Gnomad FIN exome

AF:

0.00615

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0261

AC:

38138

AN:

1461864

Hom.:

621

Cov.:

AF XY:

0.0265

AC XY:

19238

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0154

Gnomad4 AMR exome

AF:

0.0295

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.000932

Gnomad4 SAS exome

AF:

0.0347

Gnomad4 FIN exome

AF:

0.00603

Gnomad4 NFE exome

AF:

0.0277

Gnomad4 OTH exome

AF:

0.0242

GnomAD4 genome

AF:

0.0210

AC:

3197

AN:

152314

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1534

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.0327

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.0264

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0242

Hom.:

Bravo

AF:

0.0222

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0264

EpiControl

AF:

0.0282

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.8

DANN

Benign

0.66

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