16-2884316-T-C

Position:

• chr16-2884316-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138439.3(FLYWCH2):​c.-200+950T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,654 control chromosomes in the GnomAD database, including 5,903 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 0.28 (5903 hom., cov: 29)
• Consequence: FLYWCH2 NM_138439.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

Genes affected

FLYWCH2 (HGNC:25178): (FLYWCH family member 2) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLYWCH2	NM_138439.3	c.-200+950T>C		intron_variant		ENST00000396958.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLYWCH2	ENST00000396958.8	c.-200+950T>C		intron_variant		1	NM_138439.3	P2
FLYWCH2	ENST00000293981.10	c.-200+1044T>C		intron_variant		3		P2
FLYWCH2	ENST00000572006.1	c.-200+950T>C		intron_variant		2		A2
FLYWCH2	ENST00000573965.1	c.-99+950T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42225 AN: 151538 Hom.: 5897 Cov.: 29

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.279 AC: 42252 AN: 151654 Hom.: 5903 Cov.: 29 AF XY: 0.278 AC XY: 20553 AN XY: 74062

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.291

Alfa AF: 0.275 Hom.: 9724

Bravo AF: 0.280

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs2335462; hg19: chr16-2934317;