dbSNP rs1683920794: ITGA6:p.Lys36Lys (chr2-172427896-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_001394928.1(ITGA6):c.108A>G(p.Lys36Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 1,455,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

ITGA6
NM_001394928.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.76

Publications

0 publications found

Variant links:

Genes affected

ITGA6 (HGNC:6142): (integrin subunit alpha 6) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 6 subunit. This subunit may associate with a beta 1 or beta 4 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. The alpha 6 beta 4 integrin may promote tumorigenesis, while the alpha 6 beta 1 integrin may negatively regulate erbB2/HER2 signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ITGA6 Gene-Disease associations (from GenCC):

junctional epidermolysis bullosa with pyloric atresia
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
epidermolysis bullosa, junctional 6, with pyloric atresia
Inheritance: AD Classification: LIMITED Submitted by: G2P

ITGA6 links:

ENSG00000226963 (HGNC:):

ENSG00000226963 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 2-172427896-A-G is Benign according to our data. Variant chr2-172427896-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2801303.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.76 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1 link	c.108A>G	p.Lys36Lys	synonymous_variant	Exon 1 of 26	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4 link	c.108A>G	p.Lys36Lys	synonymous_variant	Exon 1 of 26	ENST00000684293.1	NP_000201.2	P23229-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6 link	c.108A>G	p.Lys36Lys	synonymous_variant	Exon 1 of 26	5	NM_001394928.1	ENSP00000406694.1		P23229-1
ITGA6	ENST00000684293.1 link	c.108A>G	p.Lys36Lys	synonymous_variant	Exon 1 of 26		NM_000210.4	ENSP00000508249.1		P23229-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000687

AC:

AN:

1455274

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

723934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32950

American (AMR)

AF:

0.00

AC:

AN:

43856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25996

East Asian (EAS)

AF:

0.00

AC:

AN:

39182

South Asian (SAS)

AF:

0.00

AC:

AN:

85320

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000901

AC:

AN:

1109338

Other (OTH)

AF:

0.00

AC:

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 07, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

1.8

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over