rs61745019

Variant names:

• chr6-40392461-C-A
• rs61745019
• NM_020737.3:c.1852G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-40392461-C-A
• chr6-40392461-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020737.3(LRFN2):​c.1852G>T​(p.Ala618Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000392 in 1,567,400 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A618T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: LRFN2 NM_020737.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.71
• Publications: 3 publications found

Genes affected

LRFN2 (HGNC:21226): (leucine rich repeat and fibronectin type III domain containing 2) Predicted to be involved in modulation of chemical synaptic transmission and regulation of postsynapse organization. Predicted to be located in plasma membrane. Predicted to be active in Schaffer collateral - CA1 synapse and cell surface. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030613005).
• BS2: High AC in GnomAd4 at 31 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020737.3. 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
	LRFN2	NM_020737.3	MANE Select	c.1852G>T	p.Ala618Ser	missense	Exon 3 of 3	NP_065788.1	Q9ULH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRFN2	ENST00000338305.7	TSL:1 MANE Select	c.1852G>T	p.Ala618Ser	missense	Exon 3 of 3	ENSP00000345985.6	Q9ULH4
	LRFN2	ENST00000700335.1		c.1852G>T	p.Ala618Ser	missense	Exon 4 of 4	ENSP00000514953.1	A0A8V8TQ63

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152248 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000165 AC: 27 AN: 163930 AF XY: 0.000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000378

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000636

Gnomad NFE exome AF: 0.000346

Gnomad OTH exome AF: 0.000665

GnomAD4 exome AF: 0.000412 AC: 583 AN: 1415152 Hom.: 1 Cov.: 34 AF XY: 0.000371 AC XY: 260 AN XY: 700296

African (AFR) AF: 0.0000932 AC: 3 AN: 32190

American (AMR) AF: 0.0000793 AC: 3 AN: 37830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25376

East Asian (EAS) AF: 0.00 AC: 0 AN: 36730

South Asian (SAS) AF: 0.00 AC: 0 AN: 81830

European-Finnish (FIN) AF: 0.000103 AC: 5 AN: 48634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.000481 AC: 523 AN: 1088270

Other (OTH) AF: 0.000836 AC: 49 AN: 58594

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74384

African (AFR) AF: 0.0000723 AC: 3 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000573 Hom.: 1

Bravo AF: 0.000204

ExAC AF: 0.000208 AC: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.24
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.74
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.5	N
PhyloP100		3.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.14
Sift	Benign	0.90	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.044
MutPred		0.14		Gain of phosphorylation at A618 (P = 0.0026)
MVP		0.46
MPC		0.30
ClinPred		0.038	T
GERP RS		2.8
Varity_R		0.047
gMVP		0.057
Mutation Taster		=95/5	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: rs61745019; hg19: chr6-40360200; COSMIC: COSV57829194;