rs2396753

Variant names:

• chr7-114508276-C-A
• rs2396753
• NM_014491.4:c.169-26341C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-114508276-C-A
• chr7-114508276-C-G
• chr7-114508276-C-T

Variant summary

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

The NM_014491.4(FOXP2):​c.169-26341C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,678 control chromosomes in the GnomAD database, including 33,352 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 0.65 (33352 hom., cov: 30)
• Consequence: FOXP2 NM_014491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• Publications: 17 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP2	NM_014491.4	c.169-26341C>A		intron_variant	Intron 2 of 16	ENST00000350908.9	NP_055306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000350908.9	c.169-26341C>A		intron_variant	Intron 2 of 16	1	NM_014491.4	ENSP00000265436.7

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99125 AN: 151560 Hom.: 33300 Cov.: 30

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.654 AC: 99236 AN: 151678 Hom.: 33352 Cov.: 30 AF XY: 0.653 AC XY: 48379 AN XY: 74110

African (AFR) AF: 0.807 AC: 33455 AN: 41434

American (AMR) AF: 0.664 AC: 10083 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3470

East Asian (EAS) AF: 0.562 AC: 2895 AN: 5152

South Asian (SAS) AF: 0.720 AC: 3469 AN: 4818

European-Finnish (FIN) AF: 0.551 AC: 5797 AN: 10522

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39825 AN: 67776

Other (OTH) AF: 0.617 AC: 1303 AN: 2112

Alfa AF: 0.607 Hom.: 5847

Bravo AF: 0.668

Asia WGS AF: 0.636 AC: 2212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.45
PhyloP100		0.13
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: rs2396753; hg19: chr7-114148331;