chr5-43039598-G-A

Position:

• chr5-43039598-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001014279.3(ANXA2R):​c.449C>T​(p.Pro150Leu) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANXA2R NM_001014279.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.451

Genes affected

ANXA2R (HGNC:33463): (annexin A2 receptor) Predicted to enable signaling receptor activity. [provided by Alliance of Genome Resources, Apr 2022]

ANXA2R-OT1 (HGNC:48996): (ANXA2R overlapping transcript 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13830203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA2R	NM_001014279.3	c.449C>T	p.Pro150Leu	missense_variant	1/1	ENST00000616064.2
ANXA2R-OT1	NR_104651.1	n.214-24448C>T		intron_variant, non_coding_transcript_variant
ANXA2R	NM_001382352.1	c.449C>T	p.Pro150Leu	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA2R	ENST00000616064.2	c.449C>T	p.Pro150Leu	missense_variant	1/1		NM_001014279.3	P1
ANXA2R-OT1	ENST00000503152.2	n.227-24448C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Jan 26, 2022

The c.449C>T (p.P150L) alteration is located in exon 1 (coding exon 1) of the ANXA2R gene. This alteration results from a C to T substitution at nucleotide position 449, causing the proline (P) at amino acid position 150 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	0.092
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.41	T;.
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.76	P;P
Vest4		0.21
MutPred		0.39		Loss of disorder (P = 0.0314);Loss of disorder (P = 0.0314);
MVP		0.26
MPC		0.45
ClinPred		0.40	T
GERP RS		1.1
Varity_R		0.11
gMVP		0.030

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr5-43039700;