rs752318393

Variant names:

• chr10-114297398-G-A
• rs752318393
• NM_001001936.3:c.2129C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-114297398-G-A
• chr10-114297398-G-C
• chr10-114297398-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001936.3(AFAP1L2):​c.2129C>T​(p.Ala710Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,612,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: AFAP1L2 NM_001001936.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16125095).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001936.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1L2	NM_001001936.3	MANE Select	c.2129C>T	p.Ala710Val	missense	Exon 17 of 19	NP_001001936.1	Q8N4X5-1
	AFAP1L2	NM_001287824.2		c.2288C>T	p.Ala763Val	missense	Exon 18 of 20	NP_001274753.1
	AFAP1L2	NM_001351065.2		c.2213C>T	p.Ala738Val	missense	Exon 18 of 20	NP_001337994.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1L2	ENST00000304129.9	TSL:1 MANE Select	c.2129C>T	p.Ala710Val	missense	Exon 17 of 19	ENSP00000303042.4	Q8N4X5-1
	AFAP1L2	ENST00000369271.7	TSL:1	c.2129C>T	p.Ala710Val	missense	Exon 17 of 19	ENSP00000358276.3	Q8N4X5-2
	AFAP1L2	ENST00000941481.1		c.2372C>T	p.Ala791Val	missense	Exon 19 of 21	ENSP00000611540.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000641 AC: 16 AN: 249454 AF XY: 0.0000815

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000708

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1460598 Hom.: 0 Cov.: 35 AF XY: 0.0000468 AC XY: 34 AN XY: 726590

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.0000447 AC: 2 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111900

Other (OTH) AF: 0.0000828 AC: 5 AN: 60386

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152086 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74300

African (AFR) AF: 0.0000966 AC: 4 AN: 41398

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000580 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.012
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.072
Sift	Benign	0.47	T
Sift4G	Benign	0.19	T
Polyphen		0.015	B
Vest4		0.28
MVP		0.41
MPC		0.15
ClinPred		0.044	T
GERP RS		5.4
Varity_R		0.16
gMVP		0.12
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs752318393; hg19: chr10-116057157; COSMIC: COSV58412261; COSMIC: COSV58412261;