12-50986572-A-AT

Position:

• chr12-50986572-A-AT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BS1_Supporting

The NM_000617.3(SLC11A2):​c.*1752_*1753insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000477 in 1,167,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.582

Genes affected

SLC11A2 (HGNC:10908): (solute carrier family 11 member 2) This gene encodes a member of the solute carrier family 11 protein family. The product of this gene transports divalent metals and is involved in iron absorption. Mutations in this gene are associated with hypochromic microcytic anemia with iron overload. A related solute carrier family 11 protein gene is located on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000427 (64/149840) while in subpopulation AMR AF= 0.00154 (23/14966). AF 95% confidence interval is 0.00105. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.*1752_*1753insA		3_prime_UTR_variant	16/16	ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.*1752_*1753insA		3_prime_UTR_variant	16/16	1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 60 AN: 149748 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00154

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000208

Gnomad OTH AF: 0.00196

GnomAD4 exome AF: 0.000484 AC: 493 AN: 1017880 Hom.: 0 Cov.: 35 AF XY: 0.000518 AC XY: 259 AN XY: 499784

Gnomad4 AFR exome AF: 0.00106

Gnomad4 AMR exome AF: 0.000890

Gnomad4 ASJ exome AF: 0.000211

Gnomad4 EAS exome AF: 0.000862

Gnomad4 SAS exome AF: 0.000488

Gnomad4 FIN exome AF: 0.0000881

Gnomad4 NFE exome AF: 0.000429

Gnomad4 OTH exome AF: 0.000997

GnomAD4 genome AF: 0.000427 AC: 64 AN: 149840 Hom.: 0 Cov.: 32 AF XY: 0.000465 AC XY: 34 AN XY: 73130

Gnomad4 AFR AF: 0.000341

Gnomad4 AMR AF: 0.00154

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000208

Gnomad4 OTH AF: 0.00194

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcytic anemia with liver iron overload Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs755515112; hg19: chr12-51380355;