chr7-151223774-G-A

Position:

chr7-151223774-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_007189.3(ABCF2):c.626C>T(p.Ser209Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,916 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ABCF2
NM_007189.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.39

Variant links:

Genes affected

ABCF2 (HGNC:71): (ATP binding cassette subfamily F member 2) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ATP-binding cassette proteins transport various molecules across extra- and intracellular membranes. Alterations in this gene may be involved in cancer progression. Related pseudogenes have been identified on chromosomes 3 and 7. [provided by RefSeq, Mar 2019]

ABCF2 links:

ABCF2-H2BK1 (HGNC:54751): (ABCF2-H2BK1 readthrough) This gene represents readthrough transcription between ABCF2 and a downstream histone H2B-like gene. [provided by RefSeq, Mar 2019]

ABCF2-H2BK1 links:

ABCF2-H2BK1 (HGNC:):

ABCF2-H2BK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCF2	NM_007189.3 linkuse as main transcript	c.626C>T	p.Ser209Leu	missense_variant	5/15	ENST00000287844.7	NP_009120.1	Q9UG63-1A0A090N7X1
ABCF2-H2BK1	NM_005692.5 linkuse as main transcript	c.626C>T	p.Ser209Leu	missense_variant	5/16		NP_005683.2	Q9UG63-2A0A090N7Y2
ABCF2-H2BK1	NR_160983.1 linkuse as main transcript	n.711C>T		non_coding_transcript_exon_variant	5/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCF2	ENST00000287844.7 linkuse as main transcript	c.626C>T	p.Ser209Leu	missense_variant	5/15	1	NM_007189.3	ENSP00000287844.2	Q9UG63-1
ABCF2-H2BK1	ENST00000222388.6 linkuse as main transcript	c.626C>T	p.Ser209Leu	missense_variant	5/16	5		ENSP00000222388.2
ABCF2	ENST00000468073.5 linkuse as main transcript	c.626C>T	p.Ser209Leu	missense_variant	4/6	2		ENSP00000419720.1	C9JZV3
ABCF2	ENST00000441774.1 linkuse as main transcript	c.626C>T	p.Ser209Leu	missense_variant	5/5	3		ENSP00000395785.1	C9JHK9

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250168

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135284

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000492

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.626C>T (p.S209L) alteration is located in exon 5 (coding exon 4) of the ABCF2 gene. This alteration results from a C to T substitution at nucleotide position 626, causing the serine (S) at amino acid position 209 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

.;D;.;.

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Uncertain

0.27

MetaRNN

Uncertain

0.67

D;D;D;D

MetaSVM

Uncertain

0.64

MutationAssessor

Benign

0.18

.;N;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.018

D;D;.;D

Polyphen

0.94

.;P;.;.

Vest4

0.84

MutPred

0.47

Loss of phosphorylation at S209 (P = 0.0167);Loss of phosphorylation at S209 (P = 0.0167);Loss of phosphorylation at S209 (P = 0.0167);Loss of phosphorylation at S209 (P = 0.0167);

MVP

0.92

MPC

1.0

ClinPred

0.62

GERP RS

5.7

Varity_R

0.60

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over