5-173233518-AAT-AATAT

Position:

• chr5-173233518-AAT-AATAT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004387.4(NKX2-5):​c.335-311_335-310dupAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 26)
• Consequence: NKX2-5 NM_004387.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

Genes affected

NKX2-5 (HGNC:2488): (NK2 homeobox 5) This gene encodes a homeobox-containing transcription factor. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases. Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKX2-5	NM_004387.4	c.335-311_335-310dupAT		intron_variant		ENST00000329198.5	NP_004378.1
NKX2-5	XM_017009071.3	c.*526_*527dupAT		3_prime_UTR_variant	2/2		XP_016864560.1
NKX2-5	NM_001166176.2	c.335-56_335-55dupAT		intron_variant			NP_001159648.1
NKX2-5	NM_001166175.2	c.335-19_335-18dupAT		intron_variant			NP_001159647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKX2-5	ENST00000329198.5	c.335-310_335-309insAT		intron_variant		1	NM_004387.4	ENSP00000327758.4
NKX2-5	ENST00000424406.2	c.335-18_335-17insAT		intron_variant		1		ENSP00000395378.2
NKX2-5	ENST00000521848.1	c.335-55_335-54insAT		intron_variant		2		ENSP00000427906.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 7

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs774726585; hg19: chr5-172660521;