7-151215058-C-T

Position:

• chr7-151215058-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_007189.3(ABCF2):​c.1555G>A​(p.Asp519Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCF2 NM_007189.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.40

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-H2BK1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCF2	NM_007189.3	c.1555G>A	p.Asp519Asn	missense_variant	14/15	ENST00000287844.7
ABCF2-H2BK1	NR_160983.1	n.1640G>A		non_coding_transcript_exon_variant	14/17
ABCF2-H2BK1	NM_005692.5	c.1555G>A	p.Asp519Asn	missense_variant	14/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCF2	ENST00000287844.7	c.1555G>A	p.Asp519Asn	missense_variant	14/15	1	NM_007189.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.1555G>A (p.D519N) alteration is located in exon 14 (coding exon 13) of the ABCF2 gene. This alteration results from a G to A substitution at nucleotide position 1555, causing the aspartic acid (D) at amino acid position 519 to be replaced by an asparagine (N). 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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.62	.;D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Benign	0.99	.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		1.0	.;D
Vest4		0.67
MutPred		0.62		Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);
MVP		0.94
MPC		1.6
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.71
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150912144;