1-16976710-G-A

Position:

• chr1-16976710-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002403.4(MFAP2):​c.239C>T​(p.Pro80Leu) variant causes a missense, splice region 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. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MFAP2 NM_002403.4 missense, splice_region
• Scores: Splicing: ADA: 0.007319
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

Genes affected

MFAP2 (HGNC:7033): (microfibril associated protein 2) Microfibrillar-associated protein 2 is a major antigen of elastin-associated microfibrils and a candidate for involvement in the etiology of inherited connective tissue diseases. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02726838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFAP2	NM_002403.4	c.239C>T	p.Pro80Leu	missense_variant, splice_region_variant	5/9	ENST00000375535.4
LOC105376806	XR_947003.3	n.702+148G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFAP2	ENST00000375535.4	c.239C>T	p.Pro80Leu	missense_variant, splice_region_variant	5/9	1	NM_002403.4	A1
	ENST00000654887.1	n.261+148G>A		intron_variant, non_coding_transcript_variant

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

Dec 27, 2022

The c.239C>T (p.P80L) alteration is located in exon 5 (coding exon 4) of the MFAP2 gene. This alteration results from a C to T substitution at nucleotide position 239, causing the proline (P) at amino acid position 80 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	Benign	0.062
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.31	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.027	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.75	.;N
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.080	N;N
REVEL	Benign	0.023
Sift	Benign	0.54	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0	.;B
Vest4		0.057
MutPred		0.33		.;Gain of catalytic residue at P80 (P = 0.0516);
MVP		0.055
MPC		0.31
ClinPred		0.039	T
GERP RS		0.28
Varity_R		0.017
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0073
dbscSNV1_RF	Benign	0.30
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-17303205;