chr10-114300246-G-C

Variant names:

• chr10-114300246-G-C
• rs144048981
• NM_001001936.3:c.1905C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001001936.3(AFAP1L2):​c.1905C>G​(p.Thr635Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,614,124 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (26 hom.)
• Consequence: AFAP1L2 NM_001001936.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.586
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-114300246-G-C is Benign according to our data. Variant chr10-114300246-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2640863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.586 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 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.1905C>G	p.Thr635Thr	synonymous	Exon 15 of 19	NP_001001936.1	Q8N4X5-1
	AFAP1L2	NM_001287824.2		c.2064C>G	p.Thr688Thr	synonymous	Exon 16 of 20	NP_001274753.1
	AFAP1L2	NM_001351065.2		c.1989C>G	p.Thr663Thr	synonymous	Exon 16 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.1905C>G	p.Thr635Thr	synonymous	Exon 15 of 19	ENSP00000303042.4	Q8N4X5-1
	AFAP1L2	ENST00000369271.7	TSL:1	c.1905C>G	p.Thr635Thr	synonymous	Exon 15 of 19	ENSP00000358276.3	Q8N4X5-2
	AFAP1L2	ENST00000941481.1		c.2148C>G	p.Thr716Thr	synonymous	Exon 17 of 21	ENSP00000611540.1

Frequencies

GnomAD3 genomes AF: 0.00345 AC: 525 AN: 152122 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00547

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00313 AC: 786 AN: 251466 AF XY: 0.00325

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00533

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00472 AC: 6906 AN: 1461884 Hom.: 26 Cov.: 30 AF XY: 0.00464 AC XY: 3377 AN XY: 727240

African (AFR) AF: 0.00105 AC: 35 AN: 33480

American (AMR) AF: 0.00237 AC: 106 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 37 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00109 AC: 94 AN: 86258

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53412

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5768

European-Non Finnish (NFE) AF: 0.00571 AC: 6345 AN: 1112010

Other (OTH) AF: 0.00394 AC: 238 AN: 60396

GnomAD4 genome AF: 0.00345 AC: 525 AN: 152240 Hom.: 2 Cov.: 33 AF XY: 0.00313 AC XY: 233 AN XY: 74434

African (AFR) AF: 0.00152 AC: 63 AN: 41548

American (AMR) AF: 0.00425 AC: 65 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00547 AC: 372 AN: 68016

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00465 Hom.: 0

Bravo AF: 0.00366

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00627

EpiControl AF: 0.00699

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	-0.80
CADD	Benign	2.2
DANN	Benign	0.31
PhyloP100		0.59
Mutation Taster		=100/0	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: rs144048981; hg19: chr10-116060005;