rs30832

Variant names:

• chr5-149981314-T-A
• rs30832
• NM_000112.4:c.1721T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-149981314-T-A
• chr5-149981314-T-C
• chr5-149981314-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_000112.4(SLC26A2):​c.1721T>A​(p.Ile574Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I574T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A2 NM_000112.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

Genes affected

SLC26A2 (HGNC:10994): (solute carrier family 26 member 2) The diastrophic dysplasia sulfate transporter is a transmembrane glycoprotein implicated in the pathogenesis of several human chondrodysplasias. It apparently is critical in cartilage for sulfation of proteoglycans and matrix organization. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a domain STAS (size 151) in uniprot entity S26A2_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_000112.4
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08228797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A2	NM_000112.4	c.1721T>A	p.Ile574Asn	missense_variant	Exon 3 of 3	ENST00000286298.5	NP_000103.2
SLC26A2	XM_017009191.3	c.1721T>A	p.Ile574Asn	missense_variant	Exon 3 of 4		XP_016864680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A2	ENST00000286298.5	c.1721T>A	p.Ile574Asn	missense_variant	Exon 3 of 3	1	NM_000112.4	ENSP00000286298.4
SLC26A2	ENST00000503336.1	c.372+2963T>A		intron_variant	Intron 1 of 1	3		ENSP00000426053.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.73
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.061	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.37		Gain of disorder (P = 0.0293);
MVP		0.87
MPC		0.075
ClinPred		0.092	T
GERP RS		4.4
Varity_R		0.11
gMVP		0.33

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: rs30832; hg19: chr5-149360877;