14-21523209-G-C

Position:

• chr14-21523209-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001364564.1(SALL2):​c.2513C>G​(p.Pro838Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,614,038 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (25 hom.)
• Consequence: SALL2 NM_001364564.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.90

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027309954).
• BP6: Variant 14-21523209-G-C is Benign according to our data. Variant chr14-21523209-G-C is described in ClinVar as [Benign]. Clinvar id is 784278.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1660/152216) while in subpopulation AFR AF= 0.0376 (1562/41520). AF 95% confidence interval is 0.0361. There are 32 homozygotes in gnomad4. There are 796 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL2	NM_001364564.1	c.2513C>G	p.Pro838Arg	missense_variant	2/2	ENST00000537235.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL2	ENST00000537235.2	c.2513C>G	p.Pro838Arg	missense_variant	2/2	2	NM_001364564.1	P3

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1661 AN: 152098 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

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: 0.000118

Gnomad OTH AF: 0.00767

GnomAD3 exomes AF: 0.00277 AC: 697 AN: 251382 Hom.: 14 AF XY: 0.00217 AC XY: 295 AN XY: 135858

Gnomad AFR exome AF: 0.0377

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00110 AC: 1602 AN: 1461822 Hom.: 25 Cov.: 34 AF XY: 0.000920 AC XY: 669 AN XY: 727206

Gnomad4 AFR exome AF: 0.0377

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000513

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.0109 AC: 1660 AN: 152216 Hom.: 32 Cov.: 32 AF XY: 0.0107 AC XY: 796 AN XY: 74418

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00759

Alfa AF: 0.00171 Hom.: 1

Bravo AF: 0.0128

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0340 AC: 150

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00358 AC: 435

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Benign	0.94
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.69	D
MetaRNN	Benign	0.0027	T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.41	T;T
Polyphen		0.063	.;B
Vest4		0.27
MVP		0.46
ClinPred		0.027	T
GERP RS		2.4
gMVP		0.35

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

Other links and lift over

dbSNP: rs61743453; hg19: chr14-21991343;