12-50986004-AT-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_000617.3(SLC11A2):c.*2320del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0081 in 1,155,402 control chromosomes in the GnomAD database, including 71 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (60 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.146

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00569 (865/151920) while in subpopulation NFE AF= 0.00927 (630/67926). AF 95% confidence interval is 0.00868. There are 11 homozygotes in gnomad4. There are 381 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
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.*2320del		3_prime_UTR_variant	16/16	ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.*2320del		3_prime_UTR_variant	16/16	1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.00569 AC: 863 AN: 151802 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00802

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00927

Gnomad OTH AF: 0.00432

GnomAD3 exomes AF: 0.00670 AC: 371 AN: 55394 Hom.: 3 AF XY: 0.00661 AC XY: 204 AN XY: 30884

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.00680

Gnomad ASJ exome AF: 0.00312

Gnomad EAS exome AF: 0.000337

Gnomad SAS exome AF: 0.00472

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.00839

GnomAD4 exome AF: 0.00847 AC: 8495 AN: 1003482 Hom.: 60 Cov.: 23 AF XY: 0.00816 AC XY: 3924 AN XY: 480630

Gnomad4 AFR exome AF: 0.00156

Gnomad4 AMR exome AF: 0.00651

Gnomad4 ASJ exome AF: 0.00235

Gnomad4 EAS exome AF: 0.000193

Gnomad4 SAS exome AF: 0.00281

Gnomad4 FIN exome AF: 0.000917

Gnomad4 NFE exome AF: 0.00932

Gnomad4 OTH exome AF: 0.00647

GnomAD4 genome AF: 0.00569 AC: 865 AN: 151920 Hom.: 11 Cov.: 32 AF XY: 0.00513 AC XY: 381 AN XY: 74236

Gnomad4 AFR AF: 0.00191

Gnomad4 AMR AF: 0.00801

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00146

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.00927

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00195 Hom.: 0

Bravo AF: 0.00599

Asia WGS AF: 0.00202 AC: 7 AN: 3478

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: rs141968385; hg19: chr12-51379787;