rs2242208

Variant names:

• chr5-180622907-G-A
• rs2242208
• NM_182925.5:c.1549-68C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-180622907-G-A
• chr5-180622907-G-C

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.1549-68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 1,069,728 control chromosomes in the GnomAD database, including 1,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (220 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1478 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.376
• Publications: 6 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=-0.79).
• BP6: Variant 5-180622907-G-A is Benign according to our data. Variant chr5-180622907-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 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.1549-68C>T		intron	N/A	NP_891555.2	P35916-2
	FLT4	NM_001354989.2		c.1549-68C>T		intron	N/A	NP_001341918.1	E9PD35
	FLT4	NM_002020.5		c.1549-68C>T		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.1549-68C>T		intron	N/A	ENSP00000261937.6	P35916-2
	FLT4	ENST00000502649.5	TSL:1	c.1549-68C>T		intron	N/A	ENSP00000426057.1	E9PD35
	FLT4	ENST00000393347.7	TSL:1	c.1549-68C>T		intron	N/A	ENSP00000377016.3	P35916-1

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 6727 AN: 145888 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.00446

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0428

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0433

GnomAD4 exome AF: 0.0449 AC: 41448 AN: 923722 Hom.: 1478 AF XY: 0.0464 AC XY: 22195 AN XY: 478826

African (AFR) AF: 0.0478 AC: 1114 AN: 23298

American (AMR) AF: 0.0330 AC: 1308 AN: 39582

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 2053 AN: 22474

East Asian (EAS) AF: 0.175 AC: 6452 AN: 36842

South Asian (SAS) AF: 0.0832 AC: 6031 AN: 72482

European-Finnish (FIN) AF: 0.0237 AC: 1122 AN: 47440

Middle Eastern (MID) AF: 0.0532 AC: 199 AN: 3742

European-Non Finnish (NFE) AF: 0.0330 AC: 20993 AN: 635386

Other (OTH) AF: 0.0512 AC: 2176 AN: 42476

GnomAD4 genome AF: 0.0461 AC: 6733 AN: 146006 Hom.: 220 Cov.: 32 AF XY: 0.0470 AC XY: 3335 AN XY: 70930

African (AFR) AF: 0.0524 AC: 2061 AN: 39336

American (AMR) AF: 0.0325 AC: 472 AN: 14518

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 323 AN: 3430

East Asian (EAS) AF: 0.184 AC: 907 AN: 4936

South Asian (SAS) AF: 0.0947 AC: 430 AN: 4542

European-Finnish (FIN) AF: 0.0238 AC: 235 AN: 9858

Middle Eastern (MID) AF: 0.0458 AC: 13 AN: 284

European-Non Finnish (NFE) AF: 0.0332 AC: 2201 AN: 66240

Other (OTH) AF: 0.0443 AC: 87 AN: 1966

Alfa AF: 0.0381 Hom.: 35

Bravo AF: 0.0461

Asia WGS AF: 0.114 AC: 394 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	-0.79
CADD	Benign	5.5
DANN	Benign	0.66
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2242208; hg19: chr5-180049907;