12-50992747-G-T

Variant names:

• chr12-50992747-G-T
• rs2018673
• NM_000617.3:c.1197+63C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000617.3(SLC11A2):​c.1197+63C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 834,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956
• Publications: 0 publications found

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]

SLC11A2 Gene-Disease associations (from GenCC):

• microcytic anemia with liver iron overload

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000617.3. 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
	SLC11A2	NM_000617.3	MANE Select	c.1197+63C>A		intron	N/A	NP_000608.1	P49281-2
	SLC11A2	NM_001379446.1		c.1284+63C>A		intron	N/A	NP_001366375.1	P49281-4
	SLC11A2	NM_001174125.2		c.1284+63C>A		intron	N/A	NP_001167596.1	P49281-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	ENST00000262052.9	TSL:1 MANE Select	c.1197+63C>A		intron	N/A	ENSP00000262052.5	P49281-2
	SLC11A2	ENST00000394904.9	TSL:1	c.1284+63C>A		intron	N/A	ENSP00000378364.3	P49281-3
	SLC11A2	ENST00000547198.5	TSL:1	c.1197+63C>A		intron	N/A	ENSP00000446769.1	P49281-1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome AF: 0.0000132 AC: 11 AN: 834154 Hom.: 0 AF XY: 0.00000957 AC XY: 4 AN XY: 417826

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17704

American (AMR) AF: 0.00 AC: 0 AN: 20666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14496

East Asian (EAS) AF: 0.00 AC: 0 AN: 26294

South Asian (SAS) AF: 0.00 AC: 0 AN: 47024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2450

European-Non Finnish (NFE) AF: 0.0000170 AC: 11 AN: 645964

Other (OTH) AF: 0.00 AC: 0 AN: 35106

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.38
DANN	Benign	0.38
PhyloP100		-0.96

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2018673;

hg19: chr12-51386530;