Genetic Variant NM_001007122.4:c.2011T>C (chr15-82759587-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001007122.4(FSD2):c.2011T>C(p.Phe671Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,426,696 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FSD2
NM_001007122.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.53

Publications

0 publications found

Variant links:

Genes affected

FSD2 (HGNC:18024): (fibronectin type III and SPRY domain containing 2) This gene encodes a protein that belongs to the FN3/SPRY family of proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

FSD2 links:

SNHG21 (HGNC:50284): (small nucleolar RNA host gene 21)

SNHG21 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007122.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FSD2	NM_001007122.4	MANE Select	c.2011T>C	p.Phe671Leu	missense	Exon 13 of 13	NP_001007123.1	A1L4K1-1
FSD2	NM_001281805.2		c.1876T>C	p.Phe626Leu	missense	Exon 13 of 13	NP_001268734.1	A1L4K1-2
FSD2	NM_001281806.2		c.1876T>C	p.Phe626Leu	missense	Exon 12 of 12	NP_001268735.1	A1L4K1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FSD2	ENST00000334574.12	TSL:1 MANE Select	c.2011T>C	p.Phe671Leu	missense	Exon 13 of 13	ENSP00000335651.8	A1L4K1-1
FSD2	ENST00000541889.1	TSL:1	c.1876T>C	p.Phe626Leu	missense	Exon 12 of 12	ENSP00000444078.1	A1L4K1-2
FSD2	ENST00000961201.1		c.2011T>C	p.Phe671Leu	missense	Exon 14 of 14	ENSP00000631260.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000489

AC:

AN:

204604

AF XY:

0.00000912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000362

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1426696

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

706088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32554

American (AMR)

AF:

0.0000259

AC:

AN:

38588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25282

East Asian (EAS)

AF:

0.00

AC:

AN:

39088

South Asian (SAS)

AF:

0.00

AC:

AN:

80660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1093740

Other (OTH)

AF:

0.0000169

AC:

AN:

59122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

PhyloP100

8.5

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.39

Sift

Benign

0.16

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.53

MutPred

0.54

Loss of sheet (P = 0.0817)

MVP

0.36

MPC

0.36

ClinPred

0.97

GERP RS

5.7

Varity_R

0.59

gMVP

0.62

Mutation Taster

=40/60

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over