rs761316361

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_014491.4(FOXP2):c.495_506delACAACAGCAGCA(p.Gln166_Gln169del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000844 in 1,611,874 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

FOXP2
NM_014491.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.77

Publications

0 publications found

Variant links:

Genes affected

FOXP2 (HGNC:13875): (forkhead box P2) This gene encodes a member of the forkhead/winged-helix (FOX) family of transcription factors. It is expressed in fetal and adult brain as well as in several other organs such as the lung and gut. The protein product contains a FOX DNA-binding domain and a large polyglutamine tract and is an evolutionarily conserved transcription factor, which may bind directly to approximately 300 to 400 gene promoters in the human genome to regulate the expression of a variety of genes. This gene is required for proper development of speech and language regions of the brain during embryogenesis, and may be involved in a variety of biological pathways and cascades that may ultimately influence language development. Mutations in this gene cause speech-language disorder 1 (SPCH1), also known as autosomal dominant speech and language disorder with orofacial dyspraxia. Multiple alternative transcripts encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

FOXP2 Gene-Disease associations (from GenCC):

specific language disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
childhood apraxia of speech
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

FOXP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_014491.4

BP6

Variant 7-114629882-GCAGCAGCAACAA-G is Benign according to our data. Variant chr7-114629882-GCAGCAGCAACAA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1744328.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP2	NM_014491.4 link	c.495_506delACAACAGCAGCA	p.Gln166_Gln169del	disruptive_inframe_deletion	Exon 5 of 17	ENST00000350908.9	NP_055306.1	O15409-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000350908.9 link	c.495_506delACAACAGCAGCA	p.Gln166_Gln169del	disruptive_inframe_deletion	Exon 5 of 17	1	NM_014491.4	ENSP00000265436.7		O15409-1

Frequencies

GnomAD3 genomes

AF:

0.0000797

AC:

AN:

150636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000847

AC:

AN:

247926

AF XY:

0.0000968

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000849

AC:

124

AN:

1461120

Hom.:

AF XY:

0.0000881

AC XY:

AN XY:

726848

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33472

American (AMR)

AF:

0.0000895

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39626

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86112

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000953

AC:

106

AN:

1111718

Other (OTH)

AF:

0.0000663

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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

AF:

0.0000796

AC:

AN:

150754

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73588

show subpopulations

African (AFR)

AF:

0.0000487

AC:

AN:

41066

American (AMR)

AF:

0.00

AC:

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5068

South Asian (SAS)

AF:

0.000212

AC:

AN:

4718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67570

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000158

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Sep 10, 2018

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.8

Mutation Taster

=117/83

disease causing (fs/PTC)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over