rs2494938

Variant names:

• chr6-40568389-G-A
• rs2494938
• NM_020737.3:c.-19+18552C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020737.3(LRFN2):​c.-19+18552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,966 control chromosomes in the GnomAD database, including 19,967 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 0.51 (19967 hom., cov: 32)
• Consequence: LRFN2 NM_020737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 42 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRFN2	NM_020737.3	c.-19+18552C>T		intron_variant	Intron 1 of 2	ENST00000338305.7	NP_065788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRFN2	ENST00000338305.7	c.-19+18552C>T		intron_variant	Intron 1 of 2	1	NM_020737.3	ENSP00000345985.6
LRFN2	ENST00000700335.1	c.-171+18552C>T		intron_variant	Intron 1 of 3			ENSP00000514953.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77171 AN: 151848 Hom.: 19950 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.521

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77219 AN: 151966 Hom.: 19967 Cov.: 32 AF XY: 0.507 AC XY: 37650 AN XY: 74294

African (AFR) AF: 0.527 AC: 21853 AN: 41432

American (AMR) AF: 0.447 AC: 6828 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2109 AN: 3464

East Asian (EAS) AF: 0.272 AC: 1404 AN: 5162

South Asian (SAS) AF: 0.580 AC: 2791 AN: 4812

European-Finnish (FIN) AF: 0.493 AC: 5206 AN: 10558

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35370 AN: 67934

Other (OTH) AF: 0.523 AC: 1104 AN: 2110

Alfa AF: 0.513 Hom.: 61347

Bravo AF: 0.496

Asia WGS AF: 0.443 AC: 1542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		1.9
Mutation Taster		=100/0	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: rs2494938; hg19: chr6-40536128;