rs2242213

Variant names:

• chr5-180621316-C-G
• rs2242213
• NM_182925.5:c.2021-64G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-180621316-C-G
• chr5-180621316-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182925.5(FLT4):​c.2021-64G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,560,584 control chromosomes in the GnomAD database, including 4,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (428 hom., cov: 33)
  • Exomes 𝑓: 0.070 (3785 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220
• Publications: 4 publications found

Genes affected

FLT4 (HGNC:3767): (fms related receptor tyrosine kinase 4) This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]

FLT4 Gene-Disease associations (from GenCC):

• congenital heart defects, multiple types, 7

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• lymphatic malformation 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• capillary infantile hemangioma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• lymphatic malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-180621316-C-G is Benign according to our data. Variant chr5-180621316-C-G is described in ClinVar as Benign. ClinVar VariationId is 1295068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182925.5. 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
	FLT4	NM_182925.5	MANE Select	c.2021-64G>C		intron	N/A	NP_891555.2	P35916-2
	FLT4	NM_001354989.2		c.2021-64G>C		intron	N/A	NP_001341918.1	E9PD35
	FLT4	NM_002020.5		c.2021-64G>C		intron	N/A	NP_002011.2	P35916-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.2021-64G>C		intron	N/A	ENSP00000261937.6	P35916-2
	FLT4	ENST00000502649.5	TSL:1	c.2021-64G>C		intron	N/A	ENSP00000426057.1	E9PD35
	FLT4	ENST00000393347.7	TSL:1	c.2021-64G>C		intron	N/A	ENSP00000377016.3	P35916-1

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9179 AN: 152056 Hom.: 428 Cov.: 33

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.0381

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0703 AC: 98943 AN: 1408406 Hom.: 3785 Cov.: 29 AF XY: 0.0704 AC XY: 48991 AN XY: 696056

African (AFR) AF: 0.00965 AC: 311 AN: 32238

American (AMR) AF: 0.0945 AC: 3873 AN: 41004

Ashkenazi Jewish (ASJ) AF: 0.0396 AC: 942 AN: 23810

East Asian (EAS) AF: 0.104 AC: 4078 AN: 39076

South Asian (SAS) AF: 0.0658 AC: 5315 AN: 80814

European-Finnish (FIN) AF: 0.103 AC: 5222 AN: 50690

Middle Eastern (MID) AF: 0.0510 AC: 282 AN: 5534

European-Non Finnish (NFE) AF: 0.0697 AC: 75122 AN: 1077228

Other (OTH) AF: 0.0655 AC: 3798 AN: 58012

GnomAD4 genome AF: 0.0603 AC: 9179 AN: 152178 Hom.: 428 Cov.: 33 AF XY: 0.0632 AC XY: 4706 AN XY: 74406

African (AFR) AF: 0.0127 AC: 529 AN: 41568

American (AMR) AF: 0.0833 AC: 1274 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0381 AC: 132 AN: 3468

East Asian (EAS) AF: 0.131 AC: 672 AN: 5138

South Asian (SAS) AF: 0.0623 AC: 301 AN: 4828

European-Finnish (FIN) AF: 0.105 AC: 1115 AN: 10604

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4970 AN: 67962

Other (OTH) AF: 0.0572 AC: 121 AN: 2114

Alfa AF: 0.0756 Hom.: 81

Bravo AF: 0.0560

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.82
CADD	Benign	4.4
DANN	Benign	0.64
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2242213; hg19: chr5-180048316; COSMIC: COSV56102203; COSMIC: COSV56102203;