chr2-149346988-T-C

Variant names:

• chr2-149346988-T-C
• rs1196694
• NM_194317.5:c.-72+16266T>C

Variant summary

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

The NM_194317.5(LYPD6):​c.-72+16266T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,952 control chromosomes in the GnomAD database, including 33,584 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 (33584 hom., cov: 32)
• Consequence: LYPD6 NM_194317.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 1 publications found

Genes affected

LYPD6 (HGNC:28751): (LY6/PLAUR domain containing 6) Members of the LY6 protein family (see SLURP1; MIM 606119), such as LYPD6, have at least one 80-amino acid LU domain that contains 10 conserved cysteines with a defined disulfide-bonding pattern (Zhang et al., 2010 [PubMed 19653121]).[supplied by OMIM, Apr 2010]

LYPD6 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYPD6	NM_194317.5	c.-72+16266T>C		intron_variant	Intron 1 of 4	ENST00000334166.9	NP_919298.1
LYPD6	XM_024452699.2	c.-21380T>C		5_prime_UTR_variant	Exon 1 of 8		XP_024308467.1
LYPD6	NM_001195685.2	c.-72+16786T>C		intron_variant	Intron 1 of 4		NP_001182614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYPD6	ENST00000334166.9	c.-72+16266T>C		intron_variant	Intron 1 of 4	1	NM_194317.5	ENSP00000334463.4
LYPD6	ENST00000418762.5	n.-72+16266T>C		intron_variant	Intron 1 of 5	1		ENSP00000396855.1
LYPD6	ENST00000409381.5	c.-72+16786T>C		intron_variant	Intron 1 of 4	2		ENSP00000386413.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99394 AN: 151834 Hom.: 33528 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.655 AC: 99506 AN: 151952 Hom.: 33584 Cov.: 32 AF XY: 0.654 AC XY: 48590 AN XY: 74278

African (AFR) AF: 0.800 AC: 33148 AN: 41410

American (AMR) AF: 0.626 AC: 9556 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2066 AN: 3470

East Asian (EAS) AF: 0.901 AC: 4631 AN: 5140

South Asian (SAS) AF: 0.636 AC: 3064 AN: 4816

European-Finnish (FIN) AF: 0.605 AC: 6392 AN: 10562

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.570 AC: 38731 AN: 67970

Other (OTH) AF: 0.644 AC: 1362 AN: 2114

Alfa AF: 0.480 Hom.: 1270

Bravo AF: 0.667

Asia WGS AF: 0.789 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.23
DANN	Benign	0.24
PhyloP100		-3.0
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: rs1196694; hg19: chr2-150203502;