14-21522069-AG-A

Variant names:

• chr14-21522069-AG-A
• rs576985829
• ENST00000611430.4:c.560delC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001291446.2(SALL2):​c.2665delC​(p.Leu889SerfsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000639 in 1,597,416 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00088 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00061 (1 hom.)
• Consequence: SALL2 NM_001291446.2 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.509
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• coloboma, ocular, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000257096 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291446.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL2	NM_001364564.1	MANE Select	c.*634delC		3_prime_UTR	Exon 2 of 2	NP_001351493.1	F5H433
	SALL2	NM_001291446.2		c.2665delC	p.Leu889SerfsTer17	frameshift	Exon 4 of 4	NP_001278375.1
	SALL2	NM_001291447.2		c.2659delC	p.Leu887SerfsTer17	frameshift	Exon 4 of 4	NP_001278376.1	E7EW59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL2	ENST00000611430.4	TSL:1	c.560delC	p.Pro187LeufsTer21	frameshift	Exon 3 of 3	ENSP00000484460.1	Q9Y467-3
	SALL2	ENST00000537235.2	TSL:2 MANE Select	c.*634delC		3_prime_UTR	Exon 2 of 2	ENSP00000438493.2	F5H433
	SALL2	ENST00000614342.1	TSL:1	c.*634delC		3_prime_UTR	Exon 2 of 2	ENSP00000483562.1	Q9Y467-1

Frequencies

GnomAD3 genomes AF: 0.000888 AC: 135 AN: 151998 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000483 AC: 111 AN: 230042 AF XY: 0.000410

Gnomad AFR exome AF: 0.00225

Gnomad AMR exome AF: 0.000264

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000571

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000521

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.000614 AC: 887 AN: 1445300 Hom.: 1 Cov.: 31 AF XY: 0.000595 AC XY: 428 AN XY: 719256

African (AFR) AF: 0.00137 AC: 46 AN: 33472

American (AMR) AF: 0.000291 AC: 13 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.000407 AC: 35 AN: 85952

European-Finnish (FIN) AF: 0.0000263 AC: 1 AN: 37992

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.000682 AC: 758 AN: 1111480

Other (OTH) AF: 0.000465 AC: 28 AN: 60240

GnomAD4 genome AF: 0.000881 AC: 134 AN: 152116 Hom.: 1 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74372

African (AFR) AF: 0.00183 AC: 76 AN: 41492

American (AMR) AF: 0.000458 AC: 7 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5166

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 67992

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.000858

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Coloboma, ocular, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51
Mutation Taster		=149/51	polymorphism

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

Other links and lift over

dbSNP: rs576985829; hg19: chr14-21990203;