14-21522874-G-A

Variant names:

• chr14-21522874-G-A
• rs766372667
• NM_001364564.1:c.2848C>T

Variant summary

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

The NM_001364564.1(SALL2):​c.2848C>T​(p.Arg950Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000354 in 1,610,370 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (1 hom.)
• Consequence: SALL2 NM_001364564.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.722
• 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_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.2848C>T	p.Arg950Trp	missense	Exon 2 of 2	NP_001351493.1	F5H433
	SALL2	NM_005407.3		c.2854C>T	p.Arg952Trp	missense	Exon 2 of 2	NP_005398.2	Q9Y467-1
	SALL2	NM_001291446.2		c.2449C>T	p.Arg817Trp	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.2848C>T	p.Arg950Trp	missense	Exon 2 of 2	ENSP00000438493.2	F5H433
	SALL2	ENST00000614342.1	TSL:1	c.2854C>T	p.Arg952Trp	missense	Exon 2 of 2	ENSP00000483562.1	Q9Y467-1
	SALL2	ENST00000611430.4	TSL:1	c.386-630C>T		intron	N/A	ENSP00000484460.1	Q9Y467-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000525 AC: 13 AN: 247640 AF XY: 0.0000672

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000377 AC: 55 AN: 1458218 Hom.: 1 Cov.: 34 AF XY: 0.0000427 AC XY: 31 AN XY: 725180

African (AFR) AF: 0.0000300 AC: 1 AN: 33350

American (AMR) AF: 0.00 AC: 0 AN: 44286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25776

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39664

South Asian (SAS) AF: 0.000256 AC: 22 AN: 85810

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1110136

Other (OTH) AF: 0.0000997 AC: 6 AN: 60176

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.018
Eigen_PC	Benign	-0.035
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.1	T
PhyloP100		0.72
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.60
MVP		0.70
ClinPred		0.73	D
GERP RS		1.8
gMVP		0.46
Mutation Taster		=92/8	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: rs766372667; hg19: chr14-21991008;