chr10-114314042-T-C

Variant names:

• chr10-114314042-T-C
• rs621375
• NM_001001936.3:c.621A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001001936.3(AFAP1L2):​c.621A>G​(p.Lys207Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,608,964 control chromosomes in the GnomAD database, including 46,353 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (10875 hom., cov: 32)
  • Exomes 𝑓: 0.20 (35478 hom.)
• Consequence: AFAP1L2 NM_001001936.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472
• Publications: 15 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]

ENSG00000299554 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.472 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

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.621A>G	p.Lys207Lys	synonymous	Exon 7 of 19	NP_001001936.1	Q8N4X5-1
	AFAP1L2	NM_001287824.2		c.780A>G	p.Lys260Lys	synonymous	Exon 8 of 20	NP_001274753.1
	AFAP1L2	NM_001351065.2		c.705A>G	p.Lys235Lys	synonymous	Exon 8 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.621A>G	p.Lys207Lys	synonymous	Exon 7 of 19	ENSP00000303042.4	Q8N4X5-1
	AFAP1L2	ENST00000369271.7	TSL:1	c.621A>G	p.Lys207Lys	synonymous	Exon 7 of 19	ENSP00000358276.3	Q8N4X5-2
	AFAP1L2	ENST00000941481.1		c.864A>G	p.Lys288Lys	synonymous	Exon 9 of 21	ENSP00000611540.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47779 AN: 151786 Hom.: 10849 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.276

GnomAD2 exomes AF: 0.224 AC: 56110 AN: 250406 AF XY: 0.226

Gnomad AFR exome AF: 0.647

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.0840

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.203 AC: 296204 AN: 1457060 Hom.: 35478 Cov.: 35 AF XY: 0.207 AC XY: 149704 AN XY: 723828

African (AFR) AF: 0.655 AC: 21888 AN: 33424

American (AMR) AF: 0.162 AC: 7210 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7091 AN: 26058

East Asian (EAS) AF: 0.150 AC: 5943 AN: 39550

South Asian (SAS) AF: 0.348 AC: 29949 AN: 86072

European-Finnish (FIN) AF: 0.154 AC: 8221 AN: 53360

Middle Eastern (MID) AF: 0.302 AC: 1735 AN: 5744

European-Non Finnish (NFE) AF: 0.181 AC: 200113 AN: 1108090

Other (OTH) AF: 0.234 AC: 14054 AN: 60188

GnomAD4 genome AF: 0.315 AC: 47853 AN: 151904 Hom.: 10875 Cov.: 32 AF XY: 0.312 AC XY: 23142 AN XY: 74238

African (AFR) AF: 0.645 AC: 26730 AN: 41438

American (AMR) AF: 0.195 AC: 2979 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3468

East Asian (EAS) AF: 0.110 AC: 564 AN: 5144

South Asian (SAS) AF: 0.353 AC: 1694 AN: 4804

European-Finnish (FIN) AF: 0.162 AC: 1707 AN: 10538

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12374 AN: 67940

Other (OTH) AF: 0.278 AC: 584 AN: 2104

Alfa AF: 0.227 Hom.: 8893

Bravo AF: 0.328

Asia WGS AF: 0.284 AC: 988 AN: 3478

EpiCase AF: 0.191

EpiControl AF: 0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.2
DANN	Benign	0.71
PhyloP100		0.47
Mutation Taster		=97/3	polymorphism (auto)

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: rs621375; hg19: chr10-116073801; COSMIC: COSV58413029;