chr14-21523010-C-G

Variant names:

• chr14-21523010-C-G
• rs61736009
• NM_001364564.1:c.2712G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001364564.1(SALL2):​c.2712G>C​(p.Glu904Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00981 in 1,614,116 control chromosomes in the GnomAD database, including 1,245 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.051 (623 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (622 hom.)
• Consequence: SALL2 NM_001364564.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.247
• Publications: 2 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: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015507042).
• BP6: Variant 14-21523010-C-G is Benign according to our data. Variant chr14-21523010-C-G is described in ClinVar as Benign. ClinVar VariationId is 2040752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364564.1. 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.2712G>C	p.Glu904Asp	missense	Exon 2 of 2	NP_001351493.1	F5H433
	SALL2	NM_005407.3		c.2718G>C	p.Glu906Asp	missense	Exon 2 of 2	NP_005398.2	Q9Y467-1
	SALL2	NM_001291446.2		c.2313G>C	p.Glu771Asp	missense	Exon 3 of 4	NP_001278375.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL2	ENST00000537235.2	TSL:2 MANE Select	c.2712G>C	p.Glu904Asp	missense	Exon 2 of 2	ENSP00000438493.2	F5H433
	SALL2	ENST00000614342.1	TSL:1	c.2718G>C	p.Glu906Asp	missense	Exon 2 of 2	ENSP00000483562.1	Q9Y467-1
	SALL2	ENST00000611430.4	TSL:1	c.386-766G>C		intron	N/A	ENSP00000484460.1	Q9Y467-3

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7748 AN: 152138 Hom.: 615 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.0351

GnomAD2 exomes AF: 0.0137 AC: 3447 AN: 251452 AF XY: 0.00995

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.00888

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000730

Gnomad OTH exome AF: 0.00847

GnomAD4 exome AF: 0.00550 AC: 8044 AN: 1461860 Hom.: 622 Cov.: 34 AF XY: 0.00482 AC XY: 3505 AN XY: 727230

African (AFR) AF: 0.184 AC: 6164 AN: 33480

American (AMR) AF: 0.0103 AC: 460 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00451 AC: 118 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000638 AC: 55 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.0117 AC: 67 AN: 5750

European-Non Finnish (NFE) AF: 0.000343 AC: 381 AN: 1112010

Other (OTH) AF: 0.0132 AC: 797 AN: 60394

GnomAD4 genome AF: 0.0512 AC: 7789 AN: 152256 Hom.: 623 Cov.: 32 AF XY: 0.0497 AC XY: 3702 AN XY: 74460

African (AFR) AF: 0.177 AC: 7338 AN: 41522

American (AMR) AF: 0.0199 AC: 305 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 68018

Other (OTH) AF: 0.0347 AC: 73 AN: 2104

Alfa AF: 0.00626 Hom.: 12

Bravo AF: 0.0580

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.166 AC: 732

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.0169 AC: 2046

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SALL2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.5
DANN	Benign	0.91
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.25
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.033
Sift	Benign	0.29	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.028
MutPred		0.25		Loss of glycosylation at P904 (P = 0.102)
ClinPred		0.0045	T
GERP RS		-0.41
gMVP		0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs61736009; hg19: chr14-21991144;