chr8-42449295-T-C

Variant names:

• chr8-42449295-T-C
• rs7832529
• NM_001257180.2:c.614-4533A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257180.2(SLC20A2):​c.614-4533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,098 control chromosomes in the GnomAD database, including 9,316 homozygotes. 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: 𝑓 0.23 (9316 hom., cov: 32)
• Consequence: SLC20A2 NM_001257180.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 3 publications found

Genes affected

SLC20A2 (HGNC:10947): (solute carrier family 20 member 2) This gene encodes a member of the inorganic phosphate transporter family. The encoded protein is a type 3 sodium-dependent phosphate symporter that plays an important role in phosphate homeostasis by mediating cellular phosphate uptake. The encoded protein also confers susceptibility to viral infection as a gamma-retroviral receptor. Mutations in this gene may play a role in familial idiopathic basal ganglia calcification. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

SLC20A2 Gene-Disease associations (from GenCC):

• basal ganglia calcification, idiopathic, 1

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257180.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC20A2	NM_001257180.2	MANE Select	c.614-4533A>G		intron	N/A	NP_001244109.1
	SLC20A2	NM_001257181.2		c.614-4533A>G		intron	N/A	NP_001244110.1
	SLC20A2	NM_006749.5		c.614-4533A>G		intron	N/A	NP_006740.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC20A2	ENST00000520262.6	TSL:2 MANE Select	c.614-4533A>G		intron	N/A	ENSP00000429754.1
	SLC20A2	ENST00000342228.7	TSL:1	c.614-4533A>G		intron	N/A	ENSP00000340465.3
	SLC20A2	ENST00000520179.5	TSL:1	c.614-4533A>G		intron	N/A	ENSP00000429712.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34645 AN: 151980 Hom.: 9269 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0459

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.228 AC: 34754 AN: 152098 Hom.: 9316 Cov.: 32 AF XY: 0.225 AC XY: 16703 AN XY: 74336

African (AFR) AF: 0.650 AC: 26950 AN: 41450

American (AMR) AF: 0.123 AC: 1874 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 274 AN: 3470

East Asian (EAS) AF: 0.154 AC: 797 AN: 5166

South Asian (SAS) AF: 0.180 AC: 867 AN: 4806

European-Finnish (FIN) AF: 0.0459 AC: 487 AN: 10612

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0448 AC: 3046 AN: 68000

Other (OTH) AF: 0.198 AC: 419 AN: 2114

Alfa AF: 0.102 Hom.: 1092

Bravo AF: 0.248

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.5
DANN	Benign	0.27
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs7832529; hg19: chr8-42306813;