10-114297241-G-A

Variant names:

• chr10-114297241-G-A
• rs140286473
• NM_001001936.3:c.2286C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001001936.3(AFAP1L2):​c.2286C>T​(p.His762His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0048 in 1,613,760 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (19 hom.)
• Consequence: AFAP1L2 NM_001001936.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.81
• Publications: 0 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 10-114297241-G-A is Benign according to our data. Variant chr10-114297241-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2640862.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.81 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.2286C>T	p.His762His	synonymous	Exon 17 of 19	NP_001001936.1	Q8N4X5-1
	AFAP1L2	NM_001287824.2		c.2445C>T	p.His815His	synonymous	Exon 18 of 20	NP_001274753.1
	AFAP1L2	NM_001351065.2		c.2370C>T	p.His790His	synonymous	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.2286C>T	p.His762His	synonymous	Exon 17 of 19	ENSP00000303042.4	Q8N4X5-1
	AFAP1L2	ENST00000369271.7	TSL:1	c.2286C>T	p.His762His	synonymous	Exon 17 of 19	ENSP00000358276.3	Q8N4X5-2
	AFAP1L2	ENST00000941481.1		c.2529C>T	p.His843His	synonymous	Exon 19 of 21	ENSP00000611540.1

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 533 AN: 151980 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00133

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00608

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00372 AC: 932 AN: 250488 AF XY: 0.00387

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.000796

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000984

Gnomad NFE exome AF: 0.00702

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00494 AC: 7221 AN: 1461666 Hom.: 19 Cov.: 36 AF XY: 0.00479 AC XY: 3485 AN XY: 727132

African (AFR) AF: 0.000866 AC: 29 AN: 33476

American (AMR) AF: 0.00203 AC: 91 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000804 AC: 21 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86250

European-Finnish (FIN) AF: 0.00116 AC: 62 AN: 53350

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.00609 AC: 6774 AN: 1111898

Other (OTH) AF: 0.00358 AC: 216 AN: 60382

GnomAD4 genome AF: 0.00350 AC: 533 AN: 152094 Hom.: 5 Cov.: 32 AF XY: 0.00309 AC XY: 230 AN XY: 74366

African (AFR) AF: 0.00145 AC: 60 AN: 41512

American (AMR) AF: 0.00170 AC: 26 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4808

European-Finnish (FIN) AF: 0.00133 AC: 14 AN: 10566

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00608 AC: 413 AN: 67974

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00428 Hom.: 0

Bravo AF: 0.00367

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00643

EpiControl AF: 0.00747

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.4
DANN	Benign	0.72
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140286473; hg19: chr10-116057000;