10-114300325-C-G

Position:

• chr10-114300325-C-G

Variant summary

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

The NM_001001936.3(AFAP1L2):​c.1826G>C​(p.Arg609Thr) 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: AFAP1L2 NM_001001936.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.278

Genes affected

AFAP1L2 (HGNC:25901): (actin filament associated protein 1 like 2) Enables SH2 domain binding activity; SH3 domain binding activity; and protein tyrosine kinase activator activity. Involved in several processes, including positive regulation of epidermal growth factor receptor signaling pathway; regulation of gene expression; and regulation of mitotic cell cycle. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.11015341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFAP1L2	NM_001001936.3	c.1826G>C	p.Arg609Thr	missense_variant	15/19	ENST00000304129.9	NP_001001936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFAP1L2	ENST00000304129.9	c.1826G>C	p.Arg609Thr	missense_variant	15/19	1	NM_001001936.3	ENSP00000303042.4
AFAP1L2	ENST00000369271.7	c.1826G>C	p.Arg609Thr	missense_variant	15/19	1		ENSP00000358276.3
AFAP1L2	ENST00000696688.1	c.1910G>C	p.Arg637Thr	missense_variant	16/20			ENSP00000512810.1
AFAP1L2	ENST00000491814.1	n.948G>C		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Nov 26, 2024

The c.1826G>C (p.R609T) alteration is located in exon 15 (coding exon 15) of the AFAP1L2 gene. This alteration results from a G to C substitution at nucleotide position 1826, causing the arginine (R) at amino acid position 609 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.4
DANN	Benign	0.82
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.038
Sift	Benign	0.17	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.24	B;B
Vest4		0.39
MVP		0.38
MPC		0.28
ClinPred		0.10	T
GERP RS		1.3
Varity_R		0.11
gMVP		0.17

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: chr10-116060084;