dbSNP rs34783571: ABCG2:p.Asp620Tyr (chr4-88092344-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004827.3(ABCG2):c.1858G>T(p.Asp620Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,698 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ABCG2
NM_004827.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.81

Publications

0 publications found

Variant links:

Genes affected

ABCG2 (HGNC:74): (ATP binding cassette subfamily G member 2 (JR blood group)) The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ABCG2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3 link	c.1858G>T	p.Asp620Tyr	missense_variant	Exon 16 of 16	ENST00000237612.8	NP_004818.2	Q9UNQ0-1A1LUE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCG2	ENST00000237612.8 link	c.1858G>T	p.Asp620Tyr	missense_variant	Exon 16 of 16	1	NM_004827.3	ENSP00000237612.3	Q9UNQ0-1
ABCG2	ENST00000515655.5 link	c.*12G>T		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000426917.1	Q9UNQ0-2
ABCG2	ENST00000650821.1 link	c.1858G>T	p.Asp620Tyr	missense_variant	Exon 17 of 17			ENSP00000498246.1	Q9UNQ0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.00

AC:

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

85796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111680

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

Eigen

Benign

0.058

Eigen_PC

Benign

0.094

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Benign

0.059

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

0.26

MutationAssessor

Uncertain

2.7

PhyloP100

4.8

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.48

Sift

Uncertain

0.025

Sift4G

Uncertain

0.0030

Polyphen

0.31

Vest4

0.60

MutPred

0.51

Gain of methylation at K616 (P = 0.0353);

MVP

0.82

MPC

0.056

ClinPred

0.94

GERP RS

4.4

Varity_R

0.55

Mutation Taster

=52/48

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over