Genetic Variant NM_001364564.1:c.2052T>C (chr14-21523670-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001364564.1(SALL2):c.2052T>C(p.Ala684Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,614,210 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 15 hom., cov: 33)

Exomes 𝑓: 0.00077 ( 12 hom. )

Consequence

SALL2
NM_001364564.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.05

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 14-21523670-A-G is Benign according to our data. Variant chr14-21523670-A-G is described in ClinVar as [Benign]. Clinvar id is 784279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00712 (1085/152324) while in subpopulation AFR AF= 0.0249 (1033/41562). AF 95% confidence interval is 0.0236. There are 15 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL2	NM_001364564.1 link	c.2052T>C	p.Ala684Ala	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.2052T>C	p.Ala684Ala	synonymous_variant	Exon 2 of 2	2	NM_001364564.1	ENSP00000438493.2		F5H433

Frequencies

GnomAD3 genomes

AF:

0.00714

AC:

1086

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

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:

0.000103

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00191

AC:

481

AN:

251294

Hom.:

AF XY:

0.00149

AC XY:

203

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0259

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000772

AC:

1129

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000650

AC XY:

473

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000638

Gnomad4 OTH exome

AF:

0.00195

GnomAD4 genome

AF:

0.00712

AC:

1085

AN:

152324

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

536

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00250

Hom.:

Bravo

AF:

0.00779

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 23, 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

-0.63

CADD

Benign

3.3

DANN

Benign

0.74

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