16-2884316-T-C

Variant names:

• chr16-2884316-T-C
• rs2335462
• NM_138439.3:c.-200+950T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

Genes affected

FLYWCH2 (HGNC:25178): (FLYWCH family member 2) Enables RNA binding activity. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138439.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLYWCH2	NM_138439.3	MANE Select	c.-200+950T>C		intron	N/A	NP_612448.1
	FLYWCH2	NM_001142499.1		c.-200+1044T>C		intron	N/A	NP_001135971.1
	FLYWCH2	NM_001142500.1		c.-200+954T>C		intron	N/A	NP_001135972.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLYWCH2	ENST00000396958.8	TSL:1 MANE Select	c.-200+950T>C		intron	N/A	ENSP00000380159.3
	FLYWCH2	ENST00000572006.1	TSL:2	c.-200+950T>C		intron	N/A	ENSP00000459223.1
	FLYWCH2	ENST00000293981.10	TSL:3	c.-200+1044T>C		intron	N/A	ENSP00000293981.6

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

African (AFR) AF: 0.281 AC: 11609 AN: 41338

American (AMR) AF: 0.296 AC: 4505 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1169 AN: 5158

South Asian (SAS) AF: 0.161 AC: 774 AN: 4816

European-Finnish (FIN) AF: 0.314 AC: 3286 AN: 10466

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 18975 AN: 67880

Other (OTH) AF: 0.291 AC: 613 AN: 2104

Alfa AF: 0.277 Hom.: 22567

Bravo AF: 0.280

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.58
PhyloP100		-0.070
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: rs2335462; hg19: chr16-2934317;