rs72559740

Variant names:

• chr11-75169368-A-T
• rs72559740
• NM_007256.5:c.644A>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_007256.5(SLCO2B1):​c.644A>T​(p.Asp215Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLCO2B1 NM_007256.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.94
• Publications: 6 publications found

Genes affected

SLCO2B1 (HGNC:10962): (solute carrier organic anion transporter family member 2B1) This locus encodes a member of the organic anion-transporting polypeptide family of membrane proteins. The protein encoded by this locus may function in regulation of placental uptake of sulfated steroids. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007256.5. 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
	SLCO2B1	NM_007256.5	MANE Select	c.644A>T	p.Asp215Val	missense	Exon 5 of 14	NP_009187.1	O94956-1
	SLCO2B1	NM_001145211.3		c.578A>T	p.Asp193Val	missense	Exon 5 of 14	NP_001138683.1	O94956-3
	SLCO2B1	NM_001145212.3		c.212A>T	p.Asp71Val	missense	Exon 2 of 11	NP_001138684.1	O94956-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO2B1	ENST00000289575.10	TSL:1 MANE Select	c.644A>T	p.Asp215Val	missense	Exon 5 of 14	ENSP00000289575.5	O94956-1
	SLCO2B1	ENST00000428359.6	TSL:1	c.578A>T	p.Asp193Val	missense	Exon 5 of 14	ENSP00000388912.2	O94956-3
	SLCO2B1	ENST00000891032.1		c.644A>T	p.Asp215Val	missense	Exon 5 of 15	ENSP00000561091.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.29	D
PhyloP100		8.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-8.6	D
REVEL	Pathogenic	0.83
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.98
MutPred		0.89		Loss of disorder (P = 0.0663)
MVP		0.85
MPC		1.0
ClinPred		1.0	D
GERP RS		4.8
gMVP		0.96
Mutation Taster		=9/91	disease causing

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: rs72559740; hg19: chr11-74880413;